The amyloid-beta (Aβ) hypothesis of Alzheimer's disease (AD) causality is now well into its third decade and is finally entering a phase of rigorous clinical testing in numerous late stage clinical trials. The...
Since the reformulation of the amyloid cascade hypothesis to focus on oligomeric aggregates of amyloid beta as the prime toxic species causing Alzheimer's disease, many researchers refocused on detecting a spe...
Authors: Kerensa Broersen, Frederic Rousseau and Joost Schymkowitz
A critical goal of Alzheimer disease research is to identify disease biomarkers that can be used in clinical trials to assist in the adjudication of treatment effects. While clinical validation remains a goal ...
Recently, it has become clear that head trauma can lead to a progressive neurodegeneration known as chronic traumatic encephalopathy. Although the medical literature also implicates head trauma as a risk facto...
Authors: Brandon E Gavett, Robert A Stern, Robert C Cantu, Christopher J Nowinski and Ann C McKee
Recent advances in biomarkers for Alzheimer's disease (AD) now allow the visualization of one of the hallmark pathologies of AD in vivo, and combination biomarker profiles can now approximate the diagnostic accur...
As Alzheimer's disease remains a clinical diagnosis, and as clinical diagnosis can be difficult, it makes sense to look for so-called biomarkers. A biomarker predicts who is likely to have the illness and who ...
Matrix metalloproteinases (MMP) are believed to be involved in the pathologic processes behind Alzheimer's disease (AD). In this study, we aimed to examine the cerebrospinal fluid (CSF) levels of MMPs and tiss...
Authors: Erik Stomrud, Maria Björkqvist, Sabina Janciauskiene, Lennart Minthon and Oskar Hansson
Evidence from clinical samples and geographically limited population studies suggests that vascular health, diabetes and apolipoprotein ε4 (APOE) are associated with dementia.
Authors: David J Llewellyn, Iain A Lang, Fiona E Matthews, Brenda L Plassman, Mary AM Rogers, Lewis B Morgenstern, Gwenith G Fisher, Mohammed U Kabeto and Kenneth M Langa
Should the apolipoprotein E (ApoE) genotype be a covariate for clinical trials in Alzheimer disease (AD)? ApoE is a transport protein for lipids, amyloid-beta proteins, and the different phenotypes differentia...
Most neurons undergo their last cell division within the first 1 to 2% of the lifespan of an organism. This has been interpreted to mean that adult neurons are permanently postmitotic, but Alzheimer's disease ...
The oldest old are the fastest growing segment of the US population but accurate estimates of the incidence of dementia in this age group have been elusive. Corrada and colleagues present data on the 5-year ag...
Clinical diagnostic accuracy using revised consensus criteria and newly developed biomarkers ranges from 65 to 96% for Alzheimer's disease (AD), with a diagnostic specificity versus other dementias of 23 to 88...
Recent advances in the clinical diagnostic instruments for diagnosing Alzheimer's disease (AD) and in neuroimaging may cast doubt in the minds of some practitioners about the continued need for neuropathology ...
Drug candidates targeting amyloid-β (Aβ) pathology in Alzheimer's disease are in different phases of clinical trials. These treatments will probably be most effective in the earlier stages of the disease, befo...
The strongest known risk factors for late-onset Alzheimer disease (LOAD) remain a positive family history and the APOE ε4 allele. van Exel and colleagues used these known risk factors to identify high- and low-ri...
The amyloid hypothesis provides a basis for the development of new therapeutic strategies in Alzheimer's disease. Two large trials have recently been published. The first is a phase 2 study of passive immunoth...
Authors: Niels D Prins, Pieter Jelle Visser and Philip Scheltens
van Exel and colleagues present an elegant study testing relationships between vascular and inflammatory traits and the risk of Alzheimer's disease (AD) development. They compared middle-aged offspring of AD c...
LY450139 (semagacestat) inhibits γ-secretase, a key enzyme for generation of amyloid β (Aβ), the peptide deposited in plaques in Alzheimer disease (AD). Previous data have shown that LY450139 lowers plasma Aβ,...
Authors: Erik Portelius, Robert A Dean, Mikael K Gustavsson, Ulf Andreasson, Henrik Zetterberg, Eric Siemers and Kaj Blennow
Since the 1990s, the genetics of Alzheimer disease (AD) has been an active area of research. The identification of deterministic mutations in the APP, PSEN1, and PSEN2 genes responsible for early-onset autosomal ...
Clinicians need to predict prognosis of Alzheimer's disease (AD), and researchers need models of progression to develop biomarkers and clinical trials designs. We tested a calculated initial progression rate t...
Authors: Rachelle S Doody, Valory Pavlik, Paul Massman, Susan Rountree, Eveleen Darby and Wenyaw Chan
Evidence for the involvement of inflammatory processes in the pathogenesis of Alzheimer's disease (AD) has been documented for a long time. However, the inflammation hypothesis in relation to AD pathology has ...
Authors: Elina Zotova, James AR Nicoll, Raj Kalaria, Clive Holmes and Delphine Boche
There are no empiric data to support guidelines for duration of therapy with antidementia drugs. This study examined whether persistent use of antidementia drugs slows clinical progression of Alzheimer disease...
Authors: Susan D Rountree, Wenyaw Chan, Valory N Pavlik, Eveleen J Darby, Samina Siddiqui and Rachelle S Doody
Amyloid is deposited in the walls of arteries and capillaries as cerebral amyloid angiopathy (CAA) in the brains of older individuals and of those with Alzheimer disease (AD). CAA in AD reflects an age-related...
Authors: Roy O Weller, Stephen D Preston, Malavika Subash and Roxana O Carare
Alzheimer's disease (AD) and a host of other neurodegenerative central nervous system (CNS) proteinopathies are characterized by the accumulation of misfolded protein aggregates. Simplistically, these aggregat...
Identifying the causes of dementia is important in the search for effective preventative and treatment strategies. The concept of mild cognitive impairment (MCI), as prodromal dementia, has been useful but rem...
Authors: Blossom CM Stephan, Fiona E Matthews, Kay-Tee Khaw, Carole Dufouil and Carol Brayne
The pathology of Alzheimer's disease (AD) features amyloid β peptide deposition, intracellular neurofibrillary tangles and deficits in the cholinergic pathway. Abnormal blood pressure is recognised as a risk f...
The field of Alzheimer's disease therapeutic research seems poised to bring to clinic the next generation of treatments, moving beyond symptomatic benefits to modification of the underlying neurobiology of the...
