Articles

Prenatal to early postnatal neurotrophic treatment prevents Alzheimer-like behavior and pathology in mice

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder of middle-aged to old individuals. The pathophysiological process of AD is believed to begin many years before the emergence of clinical sym...

Authors: Wei Wei, Yifan Wang, Yinghua Liu, Chun-Ling Dai, Yunn-Chyn Tung, Fei Liu and Khalid Iqbal

Effects of long-term sleep disruption on cognitive function and brain amyloid-β burden: a case-control study

Recent evidence indicates that disrupted sleep could contribute to the development of Alzheimer’s disease by influencing the production and/or clearance of the amyloid-β protein. We set up a case-control study...

Authors: Jana Thomas, Sharon J. Ooms, Lara J. Mentink, Jan Booij, Marcel G. M. Olde Rikkert, Sebastiaan Overeem, Roy P. C. Kessels and Jurgen A. H. R. Claassen

The two faces of synaptic failure in App^NL-G-F knock-in mice

Intensive basic and preclinical research into Alzheimer’s disease (AD) has yielded important new findings, but they could not yet been translated into effective therapies. One of the reasons is the lack of ani...

Authors: Amira Latif-Hernandez, Victor Sabanov, Tariq Ahmed, Katleen Craessaerts, Takashi Saito, Takaomi Saido and Detlef Balschun

Visual short-term memory relates to tau and amyloid burdens in preclinical autosomal dominant Alzheimer’s disease

Over the past decade, visual short-term memory (VSTM) binding tests have been shown to be one of the most sensitive behavioral indicators of Alzheimer’s disease (AD), especially when they require the binding o...

Authors: Daniel J. Norton, Mario A. Parra, Reisa A. Sperling, Ana Baena, Edmarie Guzman-Velez, David S. Jin, Nicholas Andrea, Juna Khang, Aaron Schultz, Dorene M. Rentz, Enmanuelle Pardilla-Delgado, Joshua Fuller, Keith Johnson, Eric M. Reiman, Francisco Lopera and Yakeel T. Quiroz

Repurposed agents in the Alzheimer’s disease drug development pipeline

Treatments are needed to address the growing prevalence of Alzheimer’s disease (AD). Clinical trials have failed to produce any AD drugs for Food and Drug Administration (FDA) approval since 2003, and the phar...

Authors: Justin Bauzon, Garam Lee and Jeffrey Cummings

Normalization of CSF pTau measurement by Aβ₄₀ improves its performance as a biomarker of Alzheimer’s disease

Alzheimer’s disease (AD)-related tauopathy can be measured with CSF phosphorylated tau (pTau) and tau PET. We aim to investigate the associations between these measurements and their relative ability to predic...

Authors: Tengfei Guo, Deniz Korman, Renaud La Joie, Leslie M. Shaw, John Q. Trojanowski, William J. Jagust and Susan M. Landau

Amyloid precursor protein glycosylation is altered in the brain of patients with Alzheimer’s disease

The amyloid precursor protein (APP) is a transmembrane glycoprotein that undergoes alternative proteolytic processing. Its processing through the amyloidogenic pathway originates a large sAPPβ ectodomain fragm...

Authors: Claudia P. Boix, Inmaculada Lopez-Font, Inmaculada Cuchillo-Ibañez and Javier Sáez-Valero

Aducanumab, gantenerumab, BAN2401, and ALZ-801—the first wave of amyloid-targeting drugs for Alzheimer’s disease with potential for near term approval

The body of evidence suggesting a causative, initiating role of beta amyloid (Aβ) in the pathogenesis of Alzheimer’s disease (AD) is substantial. Yet, only a few anti-amyloid agents have shown meaningful effic...

Authors: Martin Tolar, Susan Abushakra, John A. Hey, Anton Porsteinsson and Marwan Sabbagh

Estimating the potential for dementia prevention through modifiable risk factors elimination in the real-world setting: a population-based study

Preventing dementia onset is one of the global public health priorities: around 35% of dementia cases could be attributable to modifiable risk factors. These estimates relied on secondary data and did not cons...

Authors: Elena Rolandi, Daniele Zaccaria, Roberta Vaccaro, Simona Abbondanza, Laura Pettinato, Annalisa Davin and Antonio Guaita

Neurodegenerative changes in early- and late-onset cognitive impairment with and without brain amyloidosis

A substantial number of patients clinically diagnosed with Alzheimer’s disease do not harbor amyloid pathology. We analyzed the presence and extent of tau deposition and neurodegeneration in amyloid-positive (...

Authors: Eddie C. Stage Jr, Diana Svaldi, Meredith Phillips, Victor Hugo Canela, Tugce Duran, Naira Goukasian, Shannon L. Risacher, Andrew J. Saykin and Liana G. Apostolova

Association of glial and neuronal degeneration markers with Alzheimer’s disease cerebrospinal fluid profile and cognitive functions

Neuroinflammation has gained increasing attention as a potential contributing factor in the onset and progression of Alzheimer’s disease (AD). The objective of this study was to examine the association of sele...

Authors: Unnur D. Teitsdottir, Maria K. Jonsdottir, Sigrun H. Lund, Taher Darreh-Shori, Jon Snaedal and Petur H. Petersen

The contribution of vascular risk factors in neurodegenerative disorders: from mild cognitive impairment to Alzheimer’s disease

Optimization of vascular risk factor control is emerging as an alternative approach to improve cognitive outcomes in Alzheimer’s disease, although its efficacy is still under debate. We aimed to investigate th...

Authors: Yu-Wen Cheng, Ming-Jang Chiu, Ya-Fang Chen, Ting-Wen Cheng, Ya-Mei Lai and Ta-Fu Chen

Assessing what matters most to patients with or at risk for Alzheimer’s and care partners: a qualitative study evaluating symptoms, impacts, and outcomes

The What Matters Most (WMM) study was initiated to evaluate symptoms, AD-related impacts, treatment-related needs, preferences, and priorities among individuals with or at risk for Alzheimer’s disease (AD) and...

Authors: Dana B. DiBenedetti, Christina Slota, Samantha L. Wronski, George Vradenburg, Meryl Comer, Leigh F. Callahan, John Winfield, Ivana Rubino, Holly B. Krasa, Ann Hartry, Dan Wieberg, Ian N. Kremer, Debra Lappin, Allison D. Martin, Terry Frangiosa, Virginia Biggar…

Intracranial alternating current stimulation facilitates neurogenesis in a mouse model of Alzheimer’s disease

Neurogenesis is significantly impaired in the brains of both human patients and experimental animal models of Alzheimer’s disease (AD). Although deep brain stimulation promotes neurogenesis, it is an invasive ...

Authors: Qian Liu, Yihang Jiao, Weijian Yang, Beiyao Gao, Daniel K. Hsu, Jan Nolta, Michael Russell, Bruce Lyeth, Theodore P. Zanto and Min Zhao

CSF levels of the BACE1 substrate NRG1 correlate with cognition in Alzheimer’s disease

The presynaptic protein neuregulin1 (NRG1) is cleaved by beta-site APP cleaving enzyme 1 (BACE1) in a similar way as amyloid precursor protein (APP) NRG1 can activate post-synaptic receptor tyrosine-protein ki...

Authors: François Mouton-Liger, Julien Dumurgier, Emmanuel Cognat, Claire Hourregue, Henrik Zetterberg, Hugo Vanderstichele, Eugeen Vanmechelen, Elodie Bouaziz-Amar, Kaj Blennow, Jacques Hugon and Claire Paquet

Identification of potential blood biomarkers for early diagnosis of Alzheimer’s disease through RNA sequencing analysis

With demographic shifts toward older populations, the number of people with dementia is steadily increasing. Alzheimer’s disease (AD) is the most common cause of dementia, and no curative treatment is availabl...

Authors: Daichi Shigemizu, Taiki Mori, Shintaro Akiyama, Sayuri Higaki, Hiroshi Watanabe, Takashi Sakurai, Shumpei Niida and Kouichi Ozaki

The role of interleukin-33 in patients with mild cognitive impairment and Alzheimer’s disease

The neuroprotective role of interleukin (IL)-33 is supported by numerous preclinical studies, but it remains uninvestigated in clinical studies of Alzheimer’s disease (AD). We aimed to examine the association ...

Authors: Chih-Sung Liang, Kuan-Pin Su, Chia-Lin Tsai, Jiunn-Tay Lee, Che-Sheng Chu, Ta-Chuan Yeh, Ming-Wei Su, Guan-Yu Lin, Yu-Kai Lin, Hsuan-Te Chu, Chia-Kuang Tsai and Fu-Chi Yang

Cardiovascular risk factors indirectly affect acute post-stroke cognition through stroke severity and prior cognitive impairment: a moderated mediation analysis

Cognitive impairment is an important consequence of stroke and transient ischaemic attack, but its determinants are not fully understood. Simple univariable or multivariable models have not shown clinical util...

Authors: Bogna A. Drozdowska, Emma Elliott, Martin Taylor-Rowan, Robert C. Shaw, Gillian Cuthbertson, Peter Langhorne and Terence J. Quinn

Longitudinal changes in EEG power, sleep cycles and behaviour in a tau model of neurodegeneration

Disturbed sleep is associated with cognitive decline in neurodegenerative diseases such as Alzheimer’s disease (AD) and frontotemporal dementia (FTD). The progressive sequence of how neurodegeneration affects ...

Authors: C. M. Holton, N. Hanley, E. Shanks, P. Oxley, A. McCarthy, B. J. Eastwood, T. K. Murray, A. Nickerson and K. A. Wafford

CSF total tau/α-synuclein ratio improved the diagnostic performance for Alzheimer’s disease as an indicator of tau phosphorylation

Recently, several studies suggested potential involvements of α-synuclein in Alzheimer’s disease (AD) pathophysiology. Higher concentrations of α-synuclein were reported in cerebrospinal fluid (CSF) of AD pati...

Authors: Kyu Hwan Shim, Min Ju Kang, Jee Won Suh, Jung-Min Pyun, Nayoung Ryoo, Young Ho Park, Young Chul Youn, Jae-Won Jang, Jee Hyang Jeong, Kyung Won Park, Seong Hye Choi, Kyoungho Suk, Ho-Won Lee, Pan-Woo Ko, Chan-Nyoung Lee, Tae-Sung Lim…

Quantitative EEG as a biomarker in mild cognitive impairment with Lewy bodies

To investigate using quantitative EEG the (1) differences between patients with mild cognitive impairment with Lewy bodies (MCI-LB) and MCI with Alzheimer’s disease (MCI-AD) and (2) its utility as a potential ...

Authors: Julia Schumacher, John-Paul Taylor, Calum A. Hamilton, Michael Firbank, Ruth A. Cromarty, Paul C. Donaghy, Gemma Roberts, Louise Allan, Jim Lloyd, Rory Durcan, Nicola Barnett, John T. O’Brien and Alan J. Thomas

One third of dementia cases can be prevented within the next 25 years by tackling risk factors. The case “for” and “against”

Recently, it has been suggested that up to a third of the dementia cases might be preventable. While prevention is always better than cure, this is particularly important in the field of dementia, as current i...

Authors: Manuel Montero-Odasso, Zahinoor Ismail and Gill Livingston

Cathepsin D regulates cerebral Aβ42/40 ratios via differential degradation of Aβ42 and Aβ40

Cathepsin D (CatD) is a lysosomal protease that degrades both the amyloid β-protein (Aβ) and the microtubule-associated protein, tau, and has been genetically linked to late-onset Alzheimer disease (AD). Here,...

Authors: Caitlin N. Suire, Samer O. Abdul-Hay, Tomoko Sahara, Dongcheul Kang, Monica K. Brizuela, Paul Saftig, Dennis W. Dickson, Terrone L. Rosenberry and Malcolm A. Leissring

The insula, a grey matter of tastes: a volumetric MRI study in dementia with Lewy bodies

Despite the growing number of discoveries during the past decades about its functions, the insula remains a mysterious ‘island’. In addition to its involvement in basic functions such as gustation and interoce...

Authors: Nathalie Philippi, Vincent Noblet, Malik Hamdaoui, David Soulier, Anne Botzung, Emmanuelle Ehrhard, Benjamin Cretin and Frédéric Blanc

Community memory screening as a strategy for recruiting older adults into Alzheimer’s disease research

Growing awareness of Alzheimer’s disease (AD) has prompted a demand for quick and effective ways to screen for memory loss and cognitive decline in large numbers of individuals in the community. Periodic Memor...

Authors: Guerry M. Peavy, Cecily W. Jenkins, Emily A. Little, Christina Gigliotti, Amanda Calcetas, Steven D. Edland, James B. Brewer, Douglas Galasko and David P. Salmon

Imaging the aging brain: study design and baseline findings of the SENIOR cohort

Current demographic trends point towards an aging society entailing increasing occurrence and burden of neurodegenerative diseases. In this context, understanding physiological aging and its turning point into...

Authors: Alexa Haeger, Jean-François Mangin, Alexandre Vignaud, Cyril Poupon, Antoine Grigis, Fawzi Boumezbeur, Vincent Frouin, Jean-Robert Deverre, Marie Sarazin, Lucie Hertz-Pannier and Michel Bottlaender

The short-term effects of sedentary behaviour on cerebral hemodynamics and cognitive performance in older adults: a cross-over design on the potential impact of mental and/or physical activity

Sedentary behaviour might be a potential risk factor for cognitive decline. However, the short-term effects of sedentary behaviour on (cerebro) vascular and cognitive performance in older people are unknown.

Authors: Carlijn M. Maasakkers, René J. F. Melis, Roy P. C. Kessels, Paul A. Gardiner, Marcel G. M. Olde Rikkert, Dick H. J. Thijssen and Jurgen A. H. R. Claassen

Diverse proteins aggregate in mild cognitive impairment and Alzheimer’s disease brain

All cells accumulate insoluble protein aggregates throughout their lifespan. While many studies have characterized the canonical disease-associated protein aggregates, such as those associated with amyloid pla...

Authors: Devin Kepchia, Ling Huang, Richard Dargusch, Robert A. Rissman, Maxim N. Shokhirev, Wolfgang Fischer and David Schubert

The dynamics of biomarkers across the clinical spectrum of Alzheimer’s disease

Quantifying changes in the levels of biological and cognitive markers prior to the clinical presentation of Alzheimer’s disease (AD) will provide a template for understanding the underlying aetiology of the cl...

Authors: Christoforos Hadjichrysanthou, Stephanie Evans, Sumali Bajaj, Loizos C. Siakallis, Kevin McRae-McKee, Frank de Wolf and Roy M. Anderson

Optical coherence tomography angiography as a potential screening tool for cerebral small vessel diseases

The retina and the brain share anatomic, embryologic, and physiologic characteristics. Therefore, retinal imaging in patients with brain disorders has been of significant interest. Using optical coherence tomo...

Authors: Ju-Yeun Lee, Jun Pyo Kim, Hyemin Jang, Jaeho Kim, Sung Hoon Kang, Ji Sun Kim, Jongmin Lee, Young Hee Jung, Duk L. Na, Sang Won Seo, Sei Yeul Oh and Hee Jin Kim

Plasma transferrin and hemopexin are associated with altered Aβ uptake and cognitive decline in Alzheimer’s disease pathology

Heme and iron homeostasis is perturbed in Alzheimer’s disease (AD); therefore, the aim of the study was to examine the levels and association of heme with iron-binding plasma proteins in cognitively normal (CN...

Authors: Azhaar Ashraf, Nicholas J. Ashton, Pratishtha Chatterjee, Kathryn Goozee, Kaikai Shen, Jurgen Fripp, David Ames, Christopher Rowe, Colin L. Masters, Victor Villemagne, Abdul Hye, Ralph N. Martins and Po-Wah So

Correction to: Relevance of biomarkers across different neurodegenerative diseases

An amendment to this paper has been published and can be accessed via the original article.

Authors: Alexander J. Ehrenberg, Ayesha Khatun, Emma Coomans, Matthew J. Betts, Federica Capraro, Elisabeth H. Thijssen, Konstantin Senkevich, Tehmina Bharucha, Mehrsa Jafarpour, Peter N. E. Young, William Jagust, Stephen F. Carter, Tammaryn Lashley, Lea T. Grinberg, Joana B. Pereira, Niklas Mattsson-Carlgren…

Young blood plasma reduces Alzheimer’s disease-like brain pathologies and ameliorates cognitive impairment in 3×Tg-AD mice

Recent studies indicated that circulatory factors in blood plasma from young animals can reactivate neurogenesis, restore synaptic plasticity, and improve cognitive function in aged animals. Here, we investiga...

Authors: Ying Zhao, Ran Qian, Jin Zhang, Fei Liu, Khalid Iqbal, Chun-Ling Dai and Cheng-Xin Gong

Immediate and long-term consequences of COVID-19 infections for the development of neurological disease

Increasing evidence suggests that infection with Sars-CoV-2 causes neurological deficits in a substantial proportion of affected patients. While these symptoms arise acutely during the course of infection, les...

Authors: Michael T. Heneka, Douglas Golenbock, Eicke Latz, Dave Morgan and Robert Brown

Reproducibility of EEG functional connectivity in Alzheimer’s disease

Although numerous electroencephalogram (EEG) studies have described differences in functional connectivity in Alzheimer’s disease (AD) compared to healthy subjects, there is no general consensus on the methodo...

Authors: Casper T. Briels, Deborah N. Schoonhoven, Cornelis J. Stam, Hanneke de Waal, Philip Scheltens and Alida A. Gouw

A decade of Alzheimer’s Research & Therapy: reflections on the past, present, and future

Authors: Douglas Galasko and Philip Scheltens

The Alzheimer’s Prevention Initiative Composite Cognitive Test: a practical measure for tracking cognitive decline in preclinical Alzheimer’s disease

There is growing interest in identifying sensitive composite cognitive tests to serve as primary endpoints in preclinical Alzheimer’s disease (AD) treatment trials. We reported previously a composite cognitive...

Authors: Jessica B. Langbaum, Noel N. Ellison, Angelika Caputo, Ronald G. Thomas, Carolyn Langlois, Marie-Emmanuelle Riviere, Ana Graf, Cristina Lopez Lopez, Eric M. Reiman, Pierre N. Tariot and Suzanne B. Hendrix

APOE ε4 genotype-dependent cerebrospinal fluid proteomic signatures in Alzheimer’s disease

Aggregation of amyloid β into plaques in the brain is one of the earliest pathological events in Alzheimer’s disease (AD). The exact pathophysiology leading to dementia is still uncertain, but the apolipoprote...

Authors: Elles Konijnenberg, Betty M. Tijms, Johan Gobom, Valerija Dobricic, Isabelle Bos, Stephanie Vos, Magda Tsolaki, Frans Verhey, Julius Popp, Pablo Martinez-Lage, Rik Vandenberghe, Alberto Lleó, Lutz Frölich, Simon Lovestone, Johannes Streffer, Lars Bertram…

Testing whether the progression of Alzheimer’s disease changes with the year of publication, additional design, and geographical area: a modeling analysis of literature aggregate data

Our objectives were to develop a disease progression model for cognitive decline in Alzheimer’s disease (AD) and to determine whether disease progression of AD is related to the year of publication, add-on tri...

Authors: Ningyuan Zhang, Xijun Zheng, Hongxia Liu, Qingshan Zheng and Lujin Li

Partial reduction of amyloid β production by β-secretase inhibitors does not decrease synaptic transmission

Alzheimer’s disease (AD) is the most common form of age-related neurodegenerative diseases. Cerebral deposition of Aβ peptides, especially Aβ42, is considered the major neuropathological hallmark of AD and the...

Authors: Tugce Munise Satir, Lotta Agholme, Anna Karlsson, Mattias Karlsson, Paul Karila, Sebastian Illes, Petra Bergström and Henrik Zetterberg

Physical exercise during exposure to 40-Hz light flicker improves cognitive functions in the 3xTg mouse model of Alzheimer’s disease

Exercise promotes brain health and improves cognitive functioning in the elderly, while 40-Hz light flickering through the visual cortex reduces amyloid beta (Aβ) by stabilizing gamma oscillation. We examined ...

Authors: Sang-Seo Park, Hye-Sang Park, Chang-Ju Kim, Hyun-Sik Kang, Dong-Hyun Kim, Seung-Soo Baek and Tae-Woon Kim

γ-Secretase modulators exhibit selectivity for modulation of APP cleavage but inverse γ-secretase modulators do not

γ-Secretase is a multiprotein protease that cleaves amyloid protein precursor (APP) and other type I transmembrane proteins. It has two catalytic subunits, presenilins 1 and 2 (PS1 and 2). In our previous repo...

Authors: Christian B. Lessard, Edgardo Rodriguez, Thomas B. Ladd, Lisa M. Minter, Barbara A. Osborne, Lucio Miele, Todd E. Golde and Yong Ran

Is it time to use real-world data from primary care in Alzheimer’s disease?

The analysis of real-world data in clinical research is rising, but its use to study dementia subtypes has been hardly addressed. We hypothesized that real-world data might be a powerful tool to update AD epid...

Authors: Anna Ponjoan, Josep Garre-Olmo, Jordi Blanch, Ester Fages, Lia Alves-Cabratosa, Ruth Martí-Lluch, Marc Comas-Cufí, Dídac Parramon, María Garcia-Gil and Rafel Ramos

Differential blood miRNA expression in brain amyloid imaging-defined Alzheimer’s disease and controls

Peripheral blood microRNAs (miRNA) have been identified as potential biomarkers for Alzheimer’s disease (AD). Study results have generally been inconsistent and limited by sample heterogeneity. The aim of this...

Authors: Helen Zong Ying Wu, Anbupalam Thalamuthu, Lesley Cheng, Christopher Fowler, Colin L. Masters, Perminder Sachdev and Karen A. Mather

Long-term safety and tolerability of atabecestat (JNJ-54861911), an oral BACE1 inhibitor, in early Alzheimer’s disease spectrum patients: a randomized, double-blind, placebo-controlled study and a two-period extension study

Atabecestat, a potent brain-penetrable inhibitor of BACE1 activity that reduces CSF amyloid beta (Aβ), was developed for oral treatment for Alzheimer’s disease (AD).

Authors: Gerald Novak, Johannes Rolf Streffer, Maarten Timmers, David Henley, H. Robert Brashear, Jennifer Bogert, Alberto Russu, Luc Janssens, Ina Tesseur, Luc Tritsmans, Luc Van Nueten and Sebastiaan Engelborghs

The meta-memory ratio: a new cohort-independent way to measure cognitive awareness in asymptomatic individuals at risk for Alzheimer’s disease

Lack of awareness of cognitive decline (ACD) has been described at the preclinical and prodromal stages of Alzheimer’s disease (AD). In this study, we introduced a meta-memory ratio (MMR) and explored how it i...

Authors: Geoffroy Gagliardi, Marion Houot, Federica Cacciamani, Marie-Odile Habert, Bruno Dubois and Stéphane Epelbaum

Relevance of biomarkers across different neurodegenerative diseases

The panel of fluid- and imaging-based biomarkers available for neurodegenerative disease research is growing and has the potential to close important gaps in research and the clinic. With this growth and incre...

Authors: Alexander J. Ehrenberg, Ayesha Khatun, Emma Coomans, Matthew J. Betts, Federica Capraro, Elisabeth H. Thijssen, Konstantin Senkevich, Tehmina Bharucha, Mehrsa Jafarpour, Peter N. E. Young, William Jagust, Stephen F. Carter, Tammaryn Lashley, Lea T. Grinberg, Joana B. Pereira, Niklas Mattsson-Carlgren…

Longitudinal trajectories of Alzheimer’s ATN biomarkers in elderly persons without dementia

Models of Alzheimer’s disease (AD) pathophysiology posit that amyloidosis [A] precedes and accelerates tau pathology [T] that leads to neurodegeneration [N]. Besides this A-T-N sequence, other biomarker sequen...

Authors: Meng-Shan Tan, Xi Ji, Jie-Qiong Li, Wei Xu, Hui-Fu Wang, Chen-Chen Tan, Qiang Dong, Chuan-Tao Zuo, Lan Tan, John Suckling and Jin-Tai Yu

Alzheimer’s disease progression characterized by alterations in the molecular profiles and biogenesis of brain extracellular vesicles

The contributions of brain intercellular communication mechanisms, specifically extracellular vesicles (EV), to the progression of Alzheimer’s disease (AD) remain poorly understood.

Authors: Xavier Gallart-Palau, Xue Guo, Aida Serra and Siu Kwan Sze

Correction to: Sleep dysregulation, memory impairment, and CSF biomarkers during different levels of neurocognitive functioning in Alzheimer’s disease course

An amendment to this paper has been published and can be accessed via the original article.

Authors: Claudio Liguori, Fabio Placidi, Francesca Izzi, Matteo Spanetta, Nicola Biagio Mercuri and Alessandra Di Pucchio