Skip to main content

Biomarkers in biological fluids for dementia with Lewy bodies


Dementia with Lewy bodies (DLB) has become the second most common neurodegenerative dementia due to demographic ageing. Differential diagnosis is still troublesome especially in early stages of the disease, since there is a great clinical and neuropathological overlap primarily with Alzheimer's disease and Parkinson's disease. Therefore, more specific biomarkers, not only for scientific reasons but also for clinical therapeutic decision-making, are urgently needed. In this review, we summarize the knowledge on fluid biomarkers for DLB, derived predominantly from cerebrospinal fluid. We discuss the value of well-defined markers (β-amyloid, (phosphorylated) tau, ±-synuclein) as well as some promising ‘upcoming' substances, which still have to be further evaluated.


The isolation and successful detection of soluble ²-amyloid (A²) from biological fluids in 1992 [1] revolutionized our knowledge of the connection between molecular pathology and cerebrospinal fluid (CSF) biomarkers. The progressing elucidation of the underlying and overlapping molecular pathologies of several neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), has resulted in new biomarkers, which are urgently needed for more accurate diagnosis and as possible endpoints for clinical trials with future neuropreventive strategies. Thanks to vigorous defining criteria, the stratification of dementia with Lewy-bodies (DLB) as a molecular and clinical ‘in-between' disorder has been pursued, but it still has clinical and neuropathological overlap with AD and PD [2],[3], which makes its early diagnosis difficult. While hallucinations in AD predict the coincidence of DLB with a specificity of 100% [4], the presence of non-motor symptoms, decreased dopamine transporter imaging [5] and response to dopaminergic therapy does not help to separate DLB from PD since only about 36% of subjects can be clinically classified as ‘responders' using the L-dopa challenge [6],[7].

The quantification of A²1-42 in CSF in combination with total and/or phosphorylated tau protein was recently (together with positron emission tomography and structural magnetic resonance imaging) included in proposed research criteria for the clinical diagnosis of AD [8]. Here, reduced A²1-42 and increased total/phosphorylated tau protein in CSF correlate with neuropathologic features of the disease - that is, Aβ plaques and neurofibrillary tangles and neuronal loss - as well as clinical symptoms and disease intensity [9]. This CSF signature is a good predictor for cognitive decline in mild cognitive impairment [10] with high predictive value for identifying converters into overt dementia [11].

In PD, the underlying pathology is characterized by presynaptic ²-synuclein (aSyn) aggregates and synapse rarefaction. Cognitive decline in PD occurs due to various reasons leading to destruction of essential networks [12]. The main question of whether and how much AD and aSyn pathology each contribute to cognitive decline in PD remains disputable [13]. A majority of DLB patients show increased cortical 11C-PIB binding, similar to AD [14],[15]. This suggests that DLB is actually a dementia associated with both aSyn and A² pathology, thereby possibly explaining its aggressive nature. PD with dementia (PDD), in contrast, shows a reduced prevalence of amyloid plaques and lower levels of cortical 11C-PIB binding than DLB [14]-[16]. This finding suggests that the dementia of PD subjects is more likely due to a specific aSyn pathology rather than only an overlap of other pathologies, in agreement with post-mortem observations [17],[18]. Others suggest, however, that the neuropathological correlate of PDD is a combination of different pathologies rather than the severity of any single pathology [3]. In addition, it has been proposed that the presence of Aβ triggers cognitive decline and dementia in PDD and DLB, but does not directly determine its nature [19]. In this context, it should be highlighted that incidental Aβ can be detected on occasion in healthy controls as well as in older subjects with PD [15], and decreased levels of CSF Aβ1-42 have been observed in recently diagnosed PD patients [20] and in patients with and without cognitive decline [21],[22]; this suggests that amyloid pathology does not have a single causative role in dementia. Furthermore, it has been shown that PD cases without dementia, but progression of cortical amyloid, show a faster cognitive deterioration than patients who are without Aβ deposits at baseline [23]. This is supported by a recent study that showed that low levels of CSF Aβ1-42 predict early-onset cognitive decline [24].

Thus, one current major problem is the overlapping neuropathology and the as yet incompletely understood molecular constituents of the pathological changes. It is expected that in the next years many more neuropathological entities will be identified and characterized at the molecular level, which will also influence our thinking of clinical phenotyping and the selection of biomarker candidates in the future [25].

Biomarkers in dementia with Lewy bodies

In addition to imaging biomarkers (see article by Mak and colleagues within this special series [26]), biomarkers in DLB include functional marker candidates, like electroencephalography slowing [27] and the detection of rapid eye movement sleep behaviour disorder and other sleep disturbances with polysomnography [28].

Dopamine transporter imaging studies are helpful in the differential diagnosis of AD, but are expensive and not widely available. A biological fluid marker would be more widely available (when shipped to a central laboratory), cheap, and have low safety concerns. Optimal marker candidates reflect a process proximal to the specific pathology; therefore, most studies on neurodegenerative disorders rely on marker candidates in the CSF. The `CSF analytic area comprises the area of the brain directly contributing to CSF composition, which incorporates the basal ganglia and the brainstem as main sites of interest in movement disorders. aSyn pathology in DLB (and PD) has also been shown in the periphery [29], however, which could enable the detection of a marker in peripheral biological fluids; for example, in blood or saliva [30]. So far, studies have been discrepant and need further validation (see below).

Cerebrospinal fluid biomarkers in dementia with Lewy bodies

The composition and alteration of CSF proteins, which might be disease-specific, underlines the value of CSF analysis as a diagnostic tool. Nevertheless, known and potential confounding factors need to be taken into account in any biological fluid study, such as protease activity, blood contamination - which occurs in 10 to 20% of lumbar punctures - and adhesion, especially of lipophilic proteins to certain external surfaces like polypropylene and glass. The adherence of standard operating procedures is essential to avoid false positive or negative findings.

Alzheimer's disease biomarkers in dementia with Lewy bodies

The combination of decreased Aβ peptides and increased total/phosphorylated tau protein in CSF of AD subjects has shown diagnostic sensitivity and specificity above 80% in most studies [9].

Enzymatic cleavage of the 120 kDa transmembrane amyloid precursor protein leads to different fragments of the Aβ peptide [31]. Aβ seems to be important for the processing of information between neurons and is variably prone to aggregate and form plaques [32]. Amyloid plaques are found in the brain of patients with AD and DLB [31],[33] and contain primarily carboxy-terminally elongated forms of Aβ peptides, such as the fragment Aβ1-42.

As in AD, CSF levels of Aβ1-42 in DLB are regularly decreased compared to non-demented controls [34]. The correlation of decreased CSF Aβ values was shown by in vivo brain amyloid load in AD [35] but also appeared to be non-specifically decreased in other disorders without plaque pathology [36], which might be due to interindividual differences in the amount of amyloidogenic amyloid precursor protein processing. Attempts to normalize Aβ1-42 concentrations to Aβ1-40 (Aβ1-42/Aβ1-40 ratio) have been promising in terms of differentiating AD from DLB when compared with measuring these biomarkers individually [37]. Nevertheless, most studies could not define valuable cutoff scores to distinguish AD and DLB [38],[39], including one large autopsy study [40]. One reason might be the heterogeneity and possible interaction of neuropathological alterations in DLB. At least one study showed significantly lower CSF Aβ1-42 in DLB patients with senile plaques compared with DLB patients without senile plaques [41]. Another reason could be that a correlation between phosphorylated tau protein in CSF and its neuropathological equivalent (neurofibrillary tangles) was not found in patients with DLB [41].

Other fragments, isoforms and posttranslational modifications of Aβ peptides have also been proposed as CSF biomarkers for DLB. The oxidized version of Aβ1-40 (Aβ1-40ox), containing ±-helical structures [42], has been shown to be increased in DLB patients compared with PDD patients and non-demented disease controls, which recently also has been shown in autopsy-proven AD and DLB [43]. This finding has been proposed to be a pathophysiological metabolism of Aβ1-40 specific to DLB, but needs to be replicated by independent groups and using alternative approaches. Other Aβ isoforms, such as Aβ1-37 and Aβ 1-38, are still a focus of research, but need to be better characterized [42]. Further posttranslational modifications (for example, fragmented forms of Aβ) possibly reflecting more disease-specific changes are currently been investigated by different groups [44].

The natively unfolded microtubule-associated phosphoprotein 68 kDa tau is important for the stabilization of microtubules [45]. Neuronal cells in AD contain pairwise helical protein filaments (neurofibrillary tangles) [46],[47] that are insoluble, stable polymers of the low molecular weight tau protein [48].

Intracellular tau protein is elevated in CSF of AD subjects and excessively increases in conditions with rapid neuronal loss - for example, Creutzfeldt-Jakob disease. In DLB, levels of CSF tau protein are lower compared to AD [40] and higher compared to PD and PDD [49]. Interestingly, patients with a diagnosis of probable DLB according to the classification criteria [5] (which should be more accurate), tend to have even lower CSF tau protein levels [49].

Hyperphosphorylation of tau protein promotes its aggregation into neurofibrillary tangles. Some CSF studies have revealed better specificity for the discrimination of AD when using p-tau protein 181 rather than total tau protein [50]. Since the phosphorylation of tau protein in brain occurs to a lesser extent in DLB [51],[52], the quantification of phosphorylated tau species in CSF may serve as a specific marker to discriminate AD from DLB [50],[53]. Other phosphorylation sites of tau protein in CSF have been analyzed for their diagnostic value, showing similar results [54]-[57] (Table 1).

Table 1 Sumary of neuropathologic, clinical, imaging and fluid markers in dementia with Lewy bodies, Parkinson's disease and Alzheimer's disease

Parkinson's disease biomarkers in dementia with Lewy bodies

The 140 amino acid aSyn is predominantly expressed in the pre-synapses supporting the formation and transport of vesicles [58] and is the major constituent of Lewy bodies, the generally accepted pathological hallmark of PD and DLB, and it is also present in the glial cytoplasmic inclusions of multiple system atrophy [59],[60].

Full-length aSyn has been detected in extracellular biological fluids, including plasma, conditioned cell media and most recently saliva [61],[62]. The quantification of extracellular aSyn has been proposed as a potential biomarker for synuclein-related disorders: most investigators have shown a reduction of CSF total aSyn in the synuclein-related disorders PD, DLB and multiple system atrophy [63]-[65]. A rather small study, but one that strictly controlled several possible confounders (for example, blood contamination, diurnal variation, food intake, rostro-caudal CSF gradient, gender, age), showed contradictory results, with an increase of aSyn in DLB compared with healthy controls and AD patients [66]. These results need to be replicated, but possible confounding factors (for example, blood contamination, subject selection and technical/methodological differences, especially choosing the right antibodies to ensure accurate measurement of total aSyn rather than its fractions) should be even more rigorously taken into account when conducting further studies.

The underlying mechanism of decreasing CSF aSyn remains unclear to date, and could result from various scenarios, such as the reduction of aSyn release into the extracellular space due to intracellular aggregation; alteration of SNCA gene transcription [67], mRNA splicing [68] or protein processing [69]; a higher CSF flow with lower permeation of plasma aSyn into CSF; an enhanced clearance rate of aSyn from CSF [70]; or as yet unidentified factors or any combination of mechanisms [65]. Furthermore, aSyn might intracellularly aggregate in Lewy bodies and presynaptic terminals (thereby possibly decreasing the extracellular amount), since results from studies on aSyn in patients with AD have been somewhat heterogeneous, perhaps indicating a subgroup of AD patients with additional Lewy body pathology and a clear mismatch of high p-tau protein 181 and low aSyn CSF levels [71]. A possible explanation for increased CSF aSyn levels (in addition to the inverse of the mechanisms described above) might be that they partly reflect neuronal and/or axonal injury, which would be in line with a correlation of total tau values and aSyn in CSF samples of AD patients [71], although a correlation between aSyn levels and regional brain atrophy could not be detected [72].

Whereas methods for quantifying total aSyn detect mono- and oligomeric forms, an oligomer-specific aSyn assay has been established that uses the same monoclonal antibody for both capture and detection [73]. Oligomeric aSyn comprises up to 10% of the total aSyn content of CSF. Independent studies show an increase of CSF oligomeric aSyn in PD compared with AD, progressive supranuclear palsy and controls [73],[74]. Together with the reduced CSF total aSyn, the ratio of oligomeric to total aSyn had a sensitivity of 89.3% and a specificity of 90.6% for the diagnosis of PD in this study [74].

Further investigation of the specificity of the antibodies and total and oligomeric aSyn enzyme-linked immunoassay techniques are needed, as are independent studies on other posttranslationally modified aSyn species, studies quantifying CSF aSyn in longitudinal patient cohorts, as well as studies of aSyn in other biological fluids.

Neurosin, a protein suggested to cleave aSyn and thereby potentially with a major role in the pathomechanisms of diseases associated with aSyn pathology, was shown to be reduced in CSF of patients with synuclein-related disorders compared with healthy controls and patients with AD. The lowest levels have been found in patients with DLB, thereby offering a new option for a potential biomarker [75].

Other PD biomarkers in CSF have not yet been investigated in DLB, such as the multifunctional protein DJ-1 and its oxidized forms involved in many cellular processes [76]-[78], and other synaptic proteins.

Other potential biomarkers for dementia with Lewy bodies


Neurofilaments (NFs) are involved in structural integrity and cell/organelle motility along the axons and determine axon calibre. CSF levels of NFs have been found to be elevated in DLB, but no significant differences have been observed in comparison with other dementias. Therefore, NFs seem to provide only a general hint of neuronal and axonal dysfunction without differential value for separating DLB from other disorders [79]. But data are still rare. In particular, subsets of NFs need to be evaluated further, since various types of neurons are affected in the different forms of dementia, perhaps meaning that different patterns of elevated NFs are potential biomarkers for differential diagnosis of dementias. Three different subunits of NF (light (NF-L), medium (NF-M) and heavy (NF-H)) have been defined. The filament is made up of one NF-L and either NF-M or NF-H arranged head to tail [80],[81].

Fatty acid-binding proteins

Fatty acid-binding proteins (FABPs) are a family of small intracellular proteins that facilitate the transport of fatty acids between the cell membrane and different organelles [82]. Lower levels of heart-type FABP have been reported in brains from patients with Down's syndrome and AD [83]. Serum FABP levels are elevated in a quite distinct manner in DLB [84],[85].

Other potential biomarkers

On the basis of stronger pathological involvement of dopaminergic and serotonergic pathways in DLB than in AD, several neurotransmitters and their metabolites have been investigated. Reduced levels of the metabolites homovanillic acid, 5- hydroxyindolacetic acid and 3-methoxy-4-hydroxyphenylethyleneglycol have been found in DLB compared with AD [86]. Especially the latter, in combination with total tau protein, p-tau and Aβ1-42, could increase the sensitivity and specificity of discriminating those entities [87].

The chondroitinase sulphate proteoglycan Neuron glia 2 is a proteoglycan involved in several basic cellular mechanisms of pericytes as well as oligodentrocyte progenitor cells and its soluble form can be detected in CSF. Lower levels of soluble Neuron glia 2 have been found in CSF of patients with AD and DLB, but not in patients with PD or PDD, thereby implicating some kind of association with the accumulation of Aβ rather than aSyn. Results are preliminary and mechanisms far from being understood, but further investigations seem to be worthwhile [88].

Cocaine and amphetamine regulated transcript is a neuropeptide which is expressed selectively in the hypothalamus and was recently found to be present at significantly reduced levels in the CSF of DLB patients compared with controls and patients with AD [89]. Further studies are needed to confirm these preliminary data resulting from a rather small patient sample. Similarly, elevated levels of calcium and magnesium in CSF as well as of magnesium in blood were found by a Swedish study group, which used mass spectrometry to compare DLB patients with healthy controls and patients with AD [90]. These findings have to be replicated by independent groups. It is noteworthy that following our growing knowledge of molecular genetics in the field of neurodegenerative diseases, there have been high expectations that some gene products (for example, DJ-1, glucocerebrosidase) might be of use as biomarkers. Unfortunately, results have been either heterogeneous or rare in terms of DLB [91].

Finally, new diagnostic proteins might be discovered by proteomic studies. So far, some `protein peaks have been found as potential differential biomarkers, but these have either not been attributed to specific proteins [92] or have not been confirmed by further studies [93]. It is problematic that there is a lack of consistency across proteomic studies, which might be due to strong variations during sample preparation prior to the proteomic experiment itself (for example, degradation of proteins by storage material, contamination with blood) [94]. Therefore, standardized procedures are needed.


This review summarizes current studies on neurochemical marker candidates for DLB. Overall, it is clear that DLB is a disease in between AD and PD, which is supported by clinical, imaging, neuropathological and neurochemical studies. Biomarker candidates from the AD and PD fields have been tested in DLB, but only a few have been shown to more specifically reflect the underlying DLB. Most of the markers reflect neuropathological features, but as long our discrimination of PDD and DLB is based only on an arbitrary ‘one-year rule' without separation based on molecular pathology, biomarker studies with DLB subjects will be hampered [95].


This article is part of a series on Lewy Body Dementia, edited by Ian McKeith and James Galvin. Other articles in this series can be found at





Alzheimer' disease




Cerebrospinal fluid


Dementia with Lewy bodies


Fatty acid-binding protein




Parkinson's disease


Parkinson's disease with dementia


  1. 1.

    Seubert P, Vigo-Pelfrey C, Esch F, Lee M, Dovey H, Davis D, Sinha S, Schlossmacher M, Whaley J, Swindlehurst C, McCormack R, Wolfert R, Selkoe D, Lieberburg I, Schenk D: Isolation and quantification of soluble Alzheimer's beta-peptide from biological fluids. Nature. 1992, 359: 325-327. 10.1038/359325a0.

    PubMed  CAS  Article  Google Scholar 

  2. 2.

    Noe E, Marder K, Bell KL, Jacobs DM, Manly JJ, Stern Y: Comparison of dementia with Lewy bodies to Alzheimer's disease and Parkinson's disease with dementia. Mov Disord. 2004, 19: 60-67. 10.1002/mds.10633.

    PubMed  Article  Google Scholar 

  3. 3.

    Compta Y, Parkkinen L, O'Sullivan SS, Vandrovcova J, Holton JL, Collins C, Lashley T, Kallis C, Williams DR, de Silva R, Lees AJ, Revesz T: Lewy- and Alzheimer-type pathologies in Parkinson's disease dementia: which is more important?. Brain. 2011, 134: 1493-1505. 10.1093/brain/awr031.

    PubMed  PubMed Central  Article  Google Scholar 

  4. 4.

    Toledo JB, Cairns NJ, Da X, Chen K, Carter D, Fleisher A, Householder E, Ayutyanont N, Roontiva A, Bauer RJ, Eisen P, Shaw LM, Davatzikos C, Weiner MW, Reiman EM, Morris JC, Trojanowski JQ: Clinical and multimodal biomarker correlates of ADNI neuropathological findings. Acta Neuropathol Commun. 2013, 1: 65-10.1186/2051-5960-1-65.

    PubMed  PubMed Central  Article  Google Scholar 

  5. 5.

    McKeith IG, Dickson DW, Lowe J, Emre M, O'Brien JT, Feldman H, Cummings J, Duda JE, Lippa C, Perry EK, Aarsland D, Arai H, Ballard CG, Boeve B, Burn DJ, Costa D, Del Ser T, Dubois B, Galasko D, Gauthier S, Goetz CG, Gomez-Tortosa E, Halliday G, Hansen LA, Hardy J, Iwatsubo T, Kalaria RN, Kaufer D, Kenny RA, Korczyn A: Diagnosis and management of dementia with Lewy bodies: third report of the DLB consortium. Neurology. 2005, 65: 1863-1872. 10.1212/01.wnl.0000187889.17253.b1.

    PubMed  CAS  Article  Google Scholar 

  6. 6.

    Molloy S, McKeith IG, O'Brien JT, Burn DJ: The role of levodopa in the management of dementia with Lewy bodies. J Neurol Neurosurg Psychiatry. 2005, 76: 1200-1203. 10.1136/jnnp.2004.052332.

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  7. 7.

    Bonelli SB, Ransmayr G, Steffelbauer M, Lukas T, Lampl C, Deibl M: L-Dopa responsiveness in dementia with Lewy bodies, Parkinson disease with and without dementia. Neurology. 2004, 63: 376-378. 10.1212/01.WNL.0000130194.84594.96.

    PubMed  CAS  Article  Google Scholar 

  8. 8.

    Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, Delacourte A, Galasko D, Gauthier S, Jicha G, Meguro K, O'Brien J, Pasquier F, Robert P, Rossor M, Salloway S, Stern Y, Visser PJ, Scheltens P: Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurol. 2007, 6: 734-746. 10.1016/S1474-4422(07)70178-3.

    PubMed  Article  Google Scholar 

  9. 9.

    Blennow K, Hampel H, Weiner M, Zetterberg H: Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol. 2010, 6: 131-144. 10.1038/nrneurol.2010.4.

    PubMed  CAS  Article  Google Scholar 

  10. 10.

    Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L: Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol. 2006, 5: 228-234. 10.1016/S1474-4422(06)70355-6.

    PubMed  CAS  Article  Google Scholar 

  11. 11.

    Buchhave P, Minthon L, Zetterberg H, Wallin AK, Blennow K, Hansson O: Cerebrospinal fluid levels of beta-amyloid 1-42, but not of tau, are fully changed already 5 to 10 years before the onset of Alzheimer dementia. Arch Gen Psychiatry. 2012, 69: 98-106. 10.1001/archgenpsychiatry.2011.155.

    PubMed  CAS  Article  Google Scholar 

  12. 12.

    Jellinger KA: Neurobiology of cognitive impairment in Parkinson's disease. Expert Rev Neurother. 2012, 12: 1451-1466. 10.1586/ern.12.131.

    PubMed  CAS  Article  Google Scholar 

  13. 13.

    Mollenhauer B, Schulz-Schaeffer W, Schlossmacher M: Synaptic alpha-synuclein pathology as the likely cause of Parkinson's disease dementia. Lancet Neurol. 2011, 10: 68-69.

    Google Scholar 

  14. 14.

    Edison P, Rowe CC, Rinne JO, Ng S, Ahmed I, Kemppainen N, Villemagne VL, O'Keefe G, Nagren K, Chaudhury KR, Masters CL, Brooks DJ: Amyloid load in Parkinson's disease dementia and Lewy body dementia measured with [11C]PIB positron emission tomography. J Neurol Neurosurg Psychiatry. 2008, 79: 1331-1338. 10.1136/jnnp.2007.127878.

    PubMed  CAS  Article  Google Scholar 

  15. 15.

    Gomperts SN, Rentz DM, Moran E, Becker JA, Locascio JJ, Klunk WE, Mathis CA, Elmaleh DR, Shoup T, Fischman AJ, Hyman BT, Growdon JH, Johnson KA: Imaging amyloid deposition in Lewy body diseases. Neurology. 2008, 71: 903-910. 10.1212/01.wnl.0000326146.60732.d6.

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  16. 16.

    Jokinen P, Scheinin N, Aalto S, Nagren K, Savisto N, Parkkola R, Rokka J, Haaparanta M, Roytta M, Rinne JO: [(11)C]PIB-, [(18)F]FDG-PET and MRI imaging in patients with Parkinson's disease with and without dementia. Parkinsonism Relat Disord. 2010, 16: 666-670. 10.1016/j.parkreldis.2010.08.021.

    PubMed  Article  Google Scholar 

  17. 17.

    Aarsland D, Perry R, Brown A, Larsen JP, Ballard C: Neuropathology of dementia in Parkinson's disease: a prospective, community-based study. Ann Neurol. 2005, 58: 773-776. 10.1002/ana.20635.

    PubMed  Article  Google Scholar 

  18. 18.

    Kramer ML, Schulz-Schaeffer WJ: Presynaptic alpha-synuclein aggregates, not Lewy bodies, cause neurodegeneration in dementia with Lewy bodies. J Neurosci. 2007, 27: 1405-1410. 10.1523/JNEUROSCI.4564-06.2007.

    PubMed  CAS  Article  Google Scholar 

  19. 19.

    Gomperts SN, Locascio JJ, Marquie M, Santarlasci AL, Rentz DM, Maye J, Johnson KA, Growdon JH: Brain amyloid and cognition in Lewy body diseases. Mov Disord. 2012, 27: 965-973. 10.1002/mds.25048.

    PubMed  PubMed Central  Article  Google Scholar 

  20. 20.

    Alves G, Bronnick K, Aarsland D, Blennow K, Zetterberg H, Ballard C, Kurz MW, Andreasson U, Tysnes OB, Larsen JP, Mulugeta E: CSF amyloid-beta and tau proteins, and cognitive performance, in early and untreated Parkinson's disease: the Norwegian ParkWest study. J Neurol Neurosurg Psychiatry. 2010, 81: 1080-1086. 10.1136/jnnp.2009.199950.

    PubMed  Article  Google Scholar 

  21. 21.

    Compta Y, Marti MJ, Ibarretxe-Bilbao N, Junque C, Valldeoriola F, Munoz E, Ezquerra M, Rios J, Tolosa E: Cerebrospinal tau, phospho-tau, and beta-amyloid and neuropsychological functions in Parkinson's disease. Mov Disord. 2009, 24: 2203-2210. 10.1002/mds.22594.

    PubMed  Article  Google Scholar 

  22. 22.

    Montine TJ, Shi M, Quinn JF, Peskind ER, Craft S, Ginghina C, Chung KA, Kim H, Galasko DR, Jankovic J, Zabetian CP, Leverenz JB, Zhang J: CSF Abeta(42) and tau in Parkinson's disease with cognitive impairment. Mov Disord. 2010, 25: 2682-2685. 10.1002/mds.23287.

    PubMed  PubMed Central  Article  Google Scholar 

  23. 23.

    Gomperts SN, Locascio JJ, Rentz D, Santarlasci A, Marquie M, Johnson KA, Growdon JH: Amyloid is linked to cognitive decline in patients with Parkinson disease without dementia. Neurology. 2013, 80: 85-91. 10.1212/WNL.0b013e31827b1a07.

    PubMed  PubMed Central  Article  Google Scholar 

  24. 24.

    Alves G, Lange J, Blennow K, Zetterberg H, Andreasson U, Forland MG, Tysnes OB, Larsen JP, Pedersen KF: CSF Abeta42 predicts early-onset dementia in Parkinson disease. Neurology. 2014, 82: 1784-1790. 10.1212/WNL.0000000000000425.

    PubMed  CAS  Article  Google Scholar 

  25. 25.

    Borroni B, Alberici A, Archetti S, Magnani E, Di Luca M, Padovani A: New insights into biological markers of frontotemporal lobar degeneration spectrum. Curr Med Chem. 2010, 17: 1002-1009. 10.2174/092986710790820651.

    PubMed  Article  Google Scholar 

  26. 26.

    Mak E, Su L, Williams GB, O'Brien JT: Neuroimaging characteristics of dementia with Lewy bodies. Alzheimers Res Ther. 2014, 6: 18-10.1186/alzrt248.

    PubMed  PubMed Central  Article  Google Scholar 

  27. 27.

    Bonanni L, Thomas A, Tiraboschi P, Perfetti B, Varanese S, Onofrj M: EEG comparisons in early Alzheimer's disease, dementia with Lewy bodies and Parkinson's disease with dementia patients with a 2-year follow-up. Brain. 2008, 131: 690-705. 10.1093/brain/awm322.

    PubMed  Article  Google Scholar 

  28. 28.

    Terzaghi M, Arnaldi D, Rizzetti MC, Minafra B, Cremascoli R, Rustioni V, Zangaglia R, Pasotti C, Sinforiani E, Pacchetti C, Manni R: Analysis of video-polysomnographic sleep findings in dementia with Lewy bodies. Mov Disord. 2013, 28: 1416-1423.

    PubMed  Article  Google Scholar 

  29. 29.

    Braak H, de Vos RAI, Bohl J, Del Tredici K: Gastric [alpha]-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology. Neurosci Lett. 2006, 396: 67-72. 10.1016/j.neulet.2005.11.012.

    PubMed  CAS  Article  Google Scholar 

  30. 30.

    Devic I, Hwang H, Edgar JS, Izutsu K, Presland R, Pan C, Goodlett DR, Wang Y, Armaly J, Tumas V, Zabetian CP, Leverenz JB, Shi M, Zhang J: Salivary alpha-synuclein and DJ-1: potential biomarkers for Parkinson's disease. Brain. 2011, 134: e178-10.1093/brain/awr015.

    PubMed  PubMed Central  Article  Google Scholar 

  31. 31.

    Glenner GG, Wong CW, Quaranta V, Eanes ED: The amyloid deposits in Alzheimer's disease: their nature and pathogenesis. Appl Pathol. 1984, 2: 357-369.

    PubMed  CAS  Google Scholar 

  32. 32.

    Guntert A, Dobeli H, Bohrmann B: High sensitivity analysis of amyloid-beta peptide composition in amyloid deposits from human and PS2APP mouse brain. Neuroscience. 2006, 143: 461-475. 10.1016/j.neuroscience.2006.08.027.

    PubMed  CAS  Article  Google Scholar 

  33. 33.

    Jendroska K, Kashiwagi M, Sassoon J, Daniel SE: Amyloid beta-peptide and its relationship with dementia in Lewy body disease. J Neural Transm Suppl. 1997, 51: 137-144. 10.1007/978-3-7091-6846-2_11.

    PubMed  CAS  Article  Google Scholar 

  34. 34.

    Kanemaru K, Kameda N, Yamanouchi H: Decreased CSF amyloid beta42 and normal tau levels in dementia with Lewy bodies. Neurology. 2000, 54: 1875-1876. 10.1212/WNL.54.9.1875.

    PubMed  CAS  Article  Google Scholar 

  35. 35.

    Fagan AM, Mintun MA, Mach RH, Lee SY, Dence CS, Shah AR, LaRossa GN, Spinner ML, Klunk WE, Mathis CA, DeKosky ST, Morris JC, Holtzman DM: Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans. Ann Neurol. 2006, 59: 512-519. 10.1002/ana.20730.

    PubMed  CAS  Article  Google Scholar 

  36. 36.

    Mollenhauer B, Esselmann H, Roeber S, Schulz-Schaeffer WJ, Trenkwalder C, Bibl M, Steinacker P, Kretzschmar HA, Wiltfang J, Otto M: Different CSF beta-amyloid processing in Alzheimer's and Creutzfeldt-Jakob disease. J Neural Transm. 2011, 118: 691-697. 10.1007/s00702-010-0543-z.

    PubMed  CAS  Article  Google Scholar 

  37. 37.

    Nutu M, Zetterberg H, Londos E, Minthon L, Nagga K, Blennow K, Hansson O, Ohrfelt A: Evaluation of the cerebrospinal fluid amyloid-beta1-42/amyloid-beta1-40 ratio measured by alpha-LISA to distinguish Alzheimer's disease from other dementia disorders. Dement Geriatr Cogn Disord. 2013, 36: 99-110. 10.1159/000353442.

    PubMed  CAS  Article  Google Scholar 

  38. 38.

    Vanderstichele H, De Vreese K, Blennow K, Andreasen N, Sindic C, Ivanoiu A, Hampel H, Burger K, Parnetti L, Lanari A, Padovani A, DiLuca M, Blaser M, Olsson AO, Pottel H, Hulstaert F, Vanmechelen E: Analytical performance and clinical utility of the INNOTEST PHOSPHO-TAU181P assay for discrimination between Alzheimers disease and dementia with Lewy bodies. Clin Chem Lab Med. 2006, 44: 1472-1480. 10.1515/CCLM.2006.258.

    PubMed  CAS  Article  Google Scholar 

  39. 39.

    Mollenhauer B, Bibl M, Wiltfang J, Steinacker P, Ciesielczyk B, Neubert K, Trenkwalder C, Otto M: Total tau protein, phosphorylated tau (181p) protein, beta-amyloid(1-42), and beta-amyloid(1-40) in cerebrospinal fluid of patients with dementia with Lewy bodies. Clin Chem Lab Med. 2006, 44: 192-195. 10.1515/CCLM.2006.035.

    PubMed  CAS  Article  Google Scholar 

  40. 40.

    Clark CM, Xie S, Chittams J, Ewbank D, Peskind E, Galasko D, Morris JC, McKeel DW, Farlow M, Weitlauf SL, Quinn J, Kaye J, Knopman D, Arai H, Doody RS, DeCarli C, Leight S, Lee VM, Trojanowski JQ: Cerebrospinal fluid tau and beta-amyloid: how well do these biomarkers reflect autopsy-confirmed dementia diagnoses?. Arch Neurol. 2003, 60: 1696-1702. 10.1001/archneur.60.12.1696.

    PubMed  Article  Google Scholar 

  41. 41.

    Slaets S, Le Bastard N, Theuns J, Sleegers K, Verstraeten A, De Leenheir E, Luyckx J, Martin JJ, Van Broeckhoven C, Engelborghs S: Amyloid pathology influences abeta1-42 cerebrospinal fluid levels in dementia with lewy bodies. J Alzheimers Dis. 2013, 35: 137-146.

    PubMed  CAS  Google Scholar 

  42. 42.

    Bibl M, Mollenhauer B, Lewczuk P, Esselmann H, Wolf S, Trenkwalder C, Otto M, Stiens G, Ruther E, Kornhuber J, Wiltfang J: Validation of amyloid-beta peptides in CSF diagnosis of neurodegenerative dementias. Mol Psychiatry. 2007, 12: 671-680. 10.1038/

    PubMed  CAS  Article  Google Scholar 

  43. 43.

    Mollenhauer B, Esselmann H, Trenkwalder C, Schulz-Schaeffer W, Kretzschmar H, Otto M, Wiltfang J, Bibl M: CSF amyloid-beta peptides in neuropathologically diagnosed dementia with Lewy bodies and Alzheimer's disease. J Alzheimers Dis. 2011, 24: 383-391.

    PubMed  CAS  Google Scholar 

  44. 44.

    Portelius E, Brinkmalm G, Tran AJ, Zetterberg H, Westman-Brinkmalm A, Blennow K: Identification of novel APP/Abeta isoforms in human cerebrospinal fluid. Neurodegener Dis. 2009, 6: 87-94. 10.1159/000203774.

    PubMed  CAS  Article  Google Scholar 

  45. 45.

    Cleveland DW, Spiegelman BM, Kirschner MW: Conservation of microtubule associated proteins. Isolation and characterization of tau and the high molecular weight microtubule associated protein from chicken brain and from mouse fibroblasts and comparison to the corresponding mammalian brain proteins. J Biol Chem. 1979, 254: 12670-12678.

    PubMed  CAS  Google Scholar 

  46. 46.

    Braak H, Braak E, Grundke-Iqbal I, Iqbal K: Occurrence of neuropil threads in the senile human brain and in Alzheimer's disease: a third location of paired helical filaments outside of neurofibrillary tangles and neuritic plaques. Neurosci Lett. 1986, 65: 351-355. 0.1016/0304-3940(86)90288-0.

    PubMed  CAS  Article  Google Scholar 

  47. 47.

    Grundke-Iqbal I, Iqbal K, Quinlan M, Tung YC, Zaidi MS, Wisniewski HM: Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. J Biol Chem. 1986, 261: 6084-6089.

    PubMed  CAS  Google Scholar 

  48. 48.

    Lee VM, Goedert M, Trojanowski JQ: Neurodegenerative tauopathies. Annu Rev Neurosci. 2001, 24: 1121-1159. 10.1146/annurev.neuro.24.1.1121.

    PubMed  CAS  Article  Google Scholar 

  49. 49.

    Mollenhauer B, Cepek L, Bibl M, Wiltfang J, Schulz-Schaeffer WJ, Ciesielczyk B, Neumann M, Steinacker P, Kretzschmar HA, Poser S, Trenkwalder C, Otto M: Tau protein, Abeta42 and S-100B protein in cerebrospinal fluid of patients with dementia with Lewy bodies. Dement Geriatr Cogn Disord. 2005, 19: 164-170. 10.1159/000083178.

    PubMed  CAS  Article  Google Scholar 

  50. 50.

    Parnetti L, Lanari A, Amici S, Gallai V, Vanmechelen E, Hulstaert F: CSF phosphorylated tau is a possible marker for discriminating Alzheimer's disease from dementia with Lewy bodies. Phospho-Tau International Study Group. Neurol Sci. 2001, 22: 77-78. 10.1007/s100720170055.

    PubMed  CAS  Article  Google Scholar 

  51. 51.

    Merdes AR, Hansen LA, Jeste DV, Galasko D, Hofstetter CR, Ho GJ, Thal LJ, Corey-Bloom J: Influence of Alzheimer pathology on clinical diagnostic accuracy in dementia with Lewy bodies. Neurology. 2003, 60: 1586-1590. 10.1212/01.WNL.0000065889.42856.F2.

    PubMed  CAS  Article  Google Scholar 

  52. 52.

    Arima K, Hirai S, Sunohara N, Aoto K, Izumiyama Y, Ueda K, Ikeda K, Kawai M: Cellular co-localization of phosphorylated tau- and NACP/alpha-synuclein-epitopes in lewy bodies in sporadic Parkinson's disease and in dementia with Lewy bodies. Brain Res. 1999, 843: 53-61. 10.1016/S0006-8993(99)01848-X.

    PubMed  CAS  Article  Google Scholar 

  53. 53.

    Hampel H, Goernitz A, Buerger K: Advances in the development of biomarkers for Alzheimer's disease: from CSF total tau and Abeta(1-42) proteins to phosphorylated tau protein. Brain Res Bull. 2003, 61: 243-253. 10.1016/S0361-9230(03)00087-X.

    PubMed  CAS  Article  Google Scholar 

  54. 54.

    Blennow K, Wallin A, Agren H, Spenger C, Siegfried J, Vanmechelen E: Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer disease?. Mol Chem Neuropathol. 1995, 26: 231-245. 10.1007/BF02815140.

    PubMed  CAS  Article  Google Scholar 

  55. 55.

    Buerger K, Zinkowski R, Teipel SJ, Tapiola T, Arai H, Blennow K, Andreasen N, Hofmann-Kiefer K, DeBernardis J, Kerkman D, McCulloch C, Kohnken R, Padberg F, Pirttila T, Schapiro MB, Rapoport SI, Moller HJ, Davies P, Hampel H: Differential diagnosis of Alzheimer disease with cerebrospinal fluid levels of tau protein phosphorylated at threonine 231. Arch Neurol. 2002, 59: 1267-1272. 10.1001/archneur.59.8.1267.

    PubMed  Article  Google Scholar 

  56. 56.

    Hu YY, He SS, Wang XC, Duan QH, Khatoon S, Iqbal K, Grundke-Iqbal I, Wang JZ: Elevated levels of phosphorylated neurofilament proteins in cerebrospinal fluid of Alzheimer disease patients. Neurosci Lett. 2002, 320: 156-160. 10.1016/S0304-3940(02)00047-2.

    PubMed  CAS  Article  Google Scholar 

  57. 57.

    Itoh N, Arai H, Urakami K, Ishiguro K, Ohno H, Hampel H, Buerger K, Wiltfang J, Otto M, Kretzschmar H, Moeller HJ, Imagawa M, Kohno H, Nakashima K, Kuzuhara S, Sasaki H, Imahori K: Large-scale, multicenter study of cerebrospinal fluid tau protein phosphorylated at serine 199 for the antemortem diagnosis of Alzheimer's disease. Ann Neurol. 2001, 50: 150-156. 10.1002/ana.1054.

    PubMed  CAS  Article  Google Scholar 

  58. 58.

    Chandra S, Gallardo G, Fernandez-Chacon R, Schluter OM, Sudhof TC: Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration. Cell. 2005, 123: 383-396. 10.1016/j.cell.2005.09.028.

    PubMed  CAS  Article  Google Scholar 

  59. 59.

    Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M: Alpha-synuclein in Lewy bodies. Nature. 1997, 388: 839-840. 10.1038/42166.

    PubMed  CAS  Article  Google Scholar 

  60. 60.

    Gai WP, Power JH, Blumbergs PC, Blessing WW: Multiple-system atrophy: a new alpha-synuclein disease?. Lancet. 1998, 352: 547-548. 10.1016/S0140-6736(05)79256-4.

    PubMed  CAS  Article  Google Scholar 

  61. 61.

    El-Agnaf OM, Salem SA, Paleologou KE, Cooper LJ, Fullwood NJ, Gibson MJ, Curran MD, Court JA, Mann DM, Ikeda S, Cookson MR, Hardy J, Allsop D: Alpha-synuclein implicated in Parkinson's disease is present in extracellular biological fluids, including human plasma. Faseb J. 2003, 17: 1945-1947.

    PubMed  CAS  Google Scholar 

  62. 62.

    Lee HJ, Patel S, Lee SJ: Intravesicular localization and exocytosis of alpha-synuclein and its aggregates. J Neurosci. 2005, 25: 6016-6024. 10.1523/JNEUROSCI.0692-05.2005.

    PubMed  CAS  Article  Google Scholar 

  63. 63.

    Shi M, Bradner J, Hancock AM, Chung KA, Quinn JF, Peskind ER, Galasko D, Jankovic J, Zabetian CP, Kim HM, Leverenz JB, Montine TJ, Ginghina C, Kang UJ, Cain KC, Wang Y, Aasly J, Goldstein D, Zhang J: Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression. Ann Neurol. 2011, 69: 570-580. 10.1002/ana.22311.

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  64. 64.

    Aerts MB, Esselink RA, Abdo WF, Bloem BR, Verbeek MM: CSF alpha-synuclein does not differentiate between parkinsonian disorders. Neurobiol Aging. 2011, 33: 430.e1-3-

    PubMed  Google Scholar 

  65. 65.

    Mollenhauer B, El-Agnaf OM, Marcus K, Trenkwalder C, Schlossmacher MG: Quantification of alpha-synuclein in cerebrospinal fluid as a biomarker candidate: review of the literature and considerations for future studies. Biomark Med. 2010, 4: 683-699. 10.2217/bmm.10.90.

    PubMed  CAS  Article  Google Scholar 

  66. 66.

    Kapaki E, Paraskevas GP, Emmanouilidou E, Vekrellis K: The diagnostic value of CSF alpha-synuclein in the differential diagnosis of dementia with Lewy bodies vs. normal subjects and patients with Alzheimer's disease. PLoS One. 2013, 8: e81654-10.1371/journal.pone.0081654.

    PubMed  PubMed Central  Article  Google Scholar 

  67. 67.

    Cantuti-Castelvetri I, Klucken J, Ingelsson M, Ramasamy K, McLean PJ, Frosch MP, Hyman BT, Standaert DG: Alpha-synuclein and chaperones in dementia with Lewy bodies. J Neuropathol Exp Neurol. 2005, 64: 1058-1066. 10.1097/01.jnen.0000190063.90440.69.

    PubMed  CAS  Article  Google Scholar 

  68. 68.

    Beyer K, Humbert J, Ferrer A, Lao JI, Carrato C, Lopez D, Ferrer I, Ariza A: Low alpha-synuclein 126 mRNA levels in dementia with Lewy bodies and Alzheimer disease. Neuroreport. 2006, 17: 1327-1330. 10.1097/01.wnr.0000224773.66904.e7.

    PubMed  CAS  Article  Google Scholar 

  69. 69.

    Anderson JP, Walker DE, Goldstein JM, de Laat R, Banducci K, Caccavello RJ, Barbour R, Huang J, Kling K, Lee M, Diep L, Keim PS, Shen X, Chataway T, Schlossmacher MG, Seubert P, Schenk D, Sinha S, Gai WP, Chilcote TJ: Phosphorylation of Ser 129 is the dominant pathological modification of alpha-synuclein in familial and sporadic Lewy body disease. J Biol Chem. 2006, 281: 29739-29752. 10.1074/jbc.M600933200.

    PubMed  CAS  Article  Google Scholar 

  70. 70.

    Chodobski A, Szmydynger-Chodobska J: Choroid plexus: target for polypeptides and site of their synthesis. Microsc Res Tech. 2001, 52: 65-82. 10.1002/1097-0029(20010101)52:1<65::AID-JEMT9>3.0.CO;2-4.

    PubMed  CAS  Article  Google Scholar 

  71. 71.

    Toledo JB, Korff A, Shaw LM, Trojanowski JQ, Zhang J: CSF alpha-synuclein improves diagnostic and prognostic performance of CSF tau and Abeta in Alzheimer's disease. Acta Neuropathol. 2013, 126: 683-697. 10.1007/s00401-013-1148-z.

    PubMed  CAS  Article  Google Scholar 

  72. 72.

    Mattsson N, Insel P, Tosun D, Zhang J, Jack CR, Galasko D, Weiner M: Effects of baseline CSF alpha-synuclein on regional brain atrophy rates in healthy elders, mild cognitive impairment and Alzheimer's disease. PLoS One. 2013, 8: e85443-10.1371/journal.pone.0085443.

    PubMed  PubMed Central  Article  Google Scholar 

  73. 73.

    El-Agnaf OM, Salem SA, Paleologou KE, Curran MD, Gibson MJ, Court JA, Schlossmacher MG, Allsop D: Detection of oligomeric forms of alpha-synuclein protein in human plasma as a potential biomarker for Parkinson's disease. Faseb J. 2006, 20: 419-425. 10.1096/fj.03-1449com.

    PubMed  CAS  Article  Google Scholar 

  74. 74.

    Tokuda T, Qureshi MM, Ardah MT, Varghese S, Shehab SA, Kasai T, Ishigami N, Tamaoka A, Nakagawa M, El-Agnaf OM: Detection of elevated levels of {alpha}-synuclein oligomers in CSF from patients with Parkinson disease. Neurology. 2010, 75: 1766-1772. 10.1212/WNL.0b013e3181fd613b.

    PubMed  CAS  Article  Google Scholar 

  75. 75.

    Wennstrom M, Surova Y, Hall S, Nilsson C, Minthon L, Bostrom F, Hansson O, Nielsen HM: Low CSF levels of both alpha-synuclein and the alpha-synuclein cleaving enzyme neurosin in patients with synucleinopathy. PLoS One. 2013, 8: e53250-10.1371/journal.pone.0053250.

    PubMed  PubMed Central  Article  Google Scholar 

  76. 76.

    Waragai M, Wei J, Fujita M, Nakai M, Ho GJ, Masliah E, Akatsu H, Yamada T, Hashimoto M: Increased level of DJ-1 in the cerebrospinal fluids of sporadic Parkinson's disease. Biochem Biophys Res Commun. 2006, 345: 967-972. 10.1016/j.bbrc.2006.05.011.

    PubMed  CAS  Article  Google Scholar 

  77. 77.

    Hong Z, Shi M, Chung KA, Quinn JF, Peskind ER, Galasko D, Jankovic J, Zabetian CP, Leverenz JB, Baird G, Montine TJ, Hancock AM, Hwang H, Pan C, Bradner J, Kang UJ, Jensen PH, Zhang J: DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson's disease. Brain. 2010, 133: 713-726. 10.1093/brain/awq008.

    PubMed  PubMed Central  Article  Google Scholar 

  78. 78.

    Choi J, Sullards MC, Olzmann JA, Rees HD, Weintraub ST, Bostwick DE, Gearing M, Levey AI, Chin LS, Li L: Oxidative damage of DJ-1 is linked to sporadic Parkinson and Alzheimer diseases. J Biol Chem. 2006, 281: 10816-10824. 10.1074/jbc.M509079200.

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  79. 79.

    de Jong D, Jansen RW, Pijnenburg YA, van Geel WJ, Borm GF, Kremer HP, Verbeek MM: CSF neurofilament proteins in the differential diagnosis of dementia. J Neurol Neurosurg Psychiatry. 2007, 78: 936-938. 10.1136/jnnp.2006.107326.

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  80. 80.

    Ching GY, Liem RK: Assembly of type IV neuronal intermediate filaments in nonneuronal cells in the absence of preexisting cytoplasmic intermediate filaments. J Cell Biol. 1993, 122: 1323-1335. 10.1083/jcb.122.6.1323.

    PubMed  CAS  Article  Google Scholar 

  81. 81.

    Schmidt ML, Murray J, Lee VM, Hill WD, Wertkin A, Trojanowski JQ: Epitope map of neurofilament protein domains in cortical and peripheral nervous system Lewy bodies. Am J Pathol. 1991, 139: 53-65.

    PubMed  CAS  PubMed Central  Google Scholar 

  82. 82.

    Storch J, Thumser AE: Tissue-specific functions in the fatty acid-binding protein family. J Biol Chem. 2010, 285: 32679-32683. 10.1074/jbc.R110.135210.

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  83. 83.

    Cheon MS, Kim SH, Fountoulakis M, Lubec G: Heart type fatty acid binding protein (H-FABP) is decreased in brains of patients with Down syndrome and Alzheimer's disease. J Neural Transm Suppl. 2003, 67: 225-234. 10.1007/978-3-7091-6721-2_20.

    PubMed  CAS  Article  Google Scholar 

  84. 84.

    Steinacker P, Mollenhauer B, Bibl M, Cepek L, Esselmann H, Brechlin P, Lewczuk P, Poser S, Kretzschmar HA, Wiltfang J, Trenkwalder C, Otto M: Heart fatty acid binding protein as a potential diagnostic marker for neurodegenerative diseases. Neurosci Lett. 2004, 370: 36-39. 10.1016/j.neulet.2004.07.061.

    PubMed  CAS  Article  Google Scholar 

  85. 85.

    Mollenhauer B, Steinacker P, Bahn E, Bibl M, Brechlin P, Schlossmacher MG, Locascio JJ, Wiltfang J, Kretzschmar HA, Poser S, Trenkwalder C, Otto M: Serum heart-type fatty acid-binding protein and cerebrospinal fluid tau: marker candidates for dementia with Lewy bodies. Neurodegener Dis. 2007, 4: 366-375. 10.1159/000105157.

    PubMed  CAS  Article  Google Scholar 

  86. 86.

    Aerts MB, Esselink RA, Claassen JA, Abdo WF, Bloem BR, Verbeek MM: CSF tau, Abeta42, and MHPG differentiate dementia with Lewy bodies from Alzheimer's disease. J Alzheimers Dis. 2011, 27: 377-384.

    PubMed  CAS  Google Scholar 

  87. 87.

    Herbert MK, Aerts MB, Kuiperij HB, Claassen JA, Spies PE, Esselink RA, Bloem BR, Verbeek MM: Addition of MHPG to Alzheimer's disease biomarkers improves differentiation of dementia with Lewy bodies from Alzheimer's disease but not other dementias. Alzheimers Dement. 2014, 10: 448-455. 10.1016/j.jalz.2013.05.1775. e442

    PubMed  Article  Google Scholar 

  88. 88.

    Nielsen HM, Hall S, Surova Y, Nagga K, Nilsson C, Londos E, Minthon L, Hansson O, Wennstrom M: Low levels of soluble NG2 in cerebrospinal fluid from patients with dementia with Lewy bodies. J Alzheimers Dis. 2014, 40: 343-350.

    PubMed  CAS  Google Scholar 

  89. 89.

    Schultz K, Wiehager S, Nilsson K, Nielsen JE, Lindquist SG, Hjermind LE, Andersen BB, Wallin A, Nilsson C, Petersen A: Reduced CSF CART in dementia with Lewy bodies. Neurosci Lett. 2009, 453: 104-106. 10.1016/j.neulet.2009.02.008.

    PubMed  CAS  Article  Google Scholar 

  90. 90.

    Bostrom F, Hansson O, Gerhardsson L, Lundh T, Minthon L, Stomrud E, Zetterberg H, Londos E: CSF Mg and Ca as diagnostic markers for dementia with Lewy bodies. Neurobiol Aging. 2009, 30: 1265-1271. 10.1016/j.neurobiolaging.2007.10.018.

    PubMed  Article  Google Scholar 

  91. 91.

    Ho GJ, Liang W, Waragai M, Sekiyama K, Masliah E, Hashimoto M: Bridging molecular genetics and biomarkers in lewy body and related disorders. Int J Alzheimers Dis. 2011, 2011: 842475-

    PubMed  PubMed Central  Google Scholar 

  92. 92.

    Wada-Isoe K, Michio K, Imamura K, Nakaso K, Kusumi M, Kowa H, Nakashima K: Serum proteomic profiling of dementia with Lewy bodies: diagnostic potential of SELDI-TOF MS analysis. J Neural Transm. 2007, 114: 1579-1583. 10.1007/s00702-007-0794-5.

    PubMed  CAS  Article  Google Scholar 

  93. 93.

    Abdi F, Quinn JF, Jankovic J, McIntosh M, Leverenz JB, Peskind E, Nixon R, Nutt J, Chung K, Zabetian C, Samii A, Lin M, Hattan S, Pan C, Wang Y, Jin J, Zhu D, Li GJ, Liu Y, Waichunas D, Montine TJ, Zhang J: Detection of biomarkers with a multiplex quantitative proteomic platform in cerebrospinal fluid of patients with neurodegenerative disorders. J Alzheimers Dis. 2006, 9: 293-348.

    PubMed  CAS  Google Scholar 

  94. 94.

    Zhang J: Proteomics of human cerebrospinal fluid - the good, the bad, and the ugly. Proteomics Clin Appl. 2007, 1: 805-819. 10.1002/prca.200700081.

    PubMed  CAS  Article  Google Scholar 

  95. 95.

    Mollenhauer B, Schlossmacher MG: CSF synuclein: adding to the biomarker footprint of dementia with Lewy bodies. J Neurol Neurosurg Psychiatry. 2010, 81: 590-591. 10.1136/jnnp.2010.206391.

    PubMed  Article  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Brit Mollenhauer.

Additional information

Competing interests

The authors declare that they have no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Schade, S., Mollenhauer, B. Biomarkers in biological fluids for dementia with Lewy bodies. Alz Res Therapy 6, 72 (2014).

Download citation


  • Multiple System Atrophy
  • Dementia With Lewy Body
  • Dementia With Lewy Body Patient
  • Dopamine Transporter Imaging
  • Probable Dementia With Lewy Body