Amyloid-β associated volume loss occurs only in the presence of phospho-tau.
Rahul S. Desikan,Linda K. McEvoy,Wesley K. Thompson,Dominic Holland,J. Cooper Roddey,Kaj Blennow,Paul S. Aisen,James B. Brewer,Bradley T. Hyman,Anders M. Dale +9 more
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The findings indicate that Aβ‐associated volume loss occurs only in the presence of phospho‐tau in humans at risk for dementia.Abstract:
The relationship between neurodegeneration and the 2 hallmark proteins of Alzheimer's disease, amyloid-β (Aβ) and tau, is still unclear. Here, we examined 286 nondemented participants (107 cognitively normal older adults and 179 memory impaired individuals) who underwent longitudinal magnetic resonance (MR) imaging and lumbar puncture. Using mixed effects models, we investigated the relationship between longitudinal entorhinal cortex atrophy rate, cerebrospinal fluid (CSF) p-tau(181p) and CSF Aβ(1-42) . We found a significant relationship between elevated entorhinal cortex atrophy rate and decreased CSF Aβ(1-42) only with elevated CSF p-tau(181p) . Our findings indicate that Aβ-associated volume loss occurs only in the presence of phospho-tau in humans at risk for dementia.read more
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Biomarker Modeling of Alzheimer’s Disease
TL;DR: Several time-dependent models of AD are discussed that take into consideration varying age of onset (early versus late) and the influence of aging and co-occurring brain pathologies that commonly arise in the elderly.
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What is normal in normal aging? Effects of aging, amyloid and Alzheimer's disease on the cerebral cortex and the hippocampus
TL;DR: It will be difficult to understand AD without understanding why it preferably affects older brains, and that a model that accounts for age-related changes in AD-vulnerable regions independently of AD-pathology is needed.
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The Evolution of Preclinical Alzheimer’s Disease: Implications for Prevention Trials
TL;DR: Recent progress in cognitive, imaging, and biomarker outcomes in the field of preclinical Alzheimer's disease, and the remaining gaps in knowledge are highlighted.
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Synergy between amyloid-β and tau in Alzheimer’s disease
TL;DR: Emerging evidence for an interaction between Aβ and tau during Alzheimer’s disease (AD) progression that challenges the classical linear trajectory model and offers a new perspective on AD pathophysiology and therapy is reviewed.
Journal ArticleDOI
Prediction of conversion from mild cognitive impairment to Alzheimer's disease dementia based upon biomarkers and neuropsychological test performance
Michael Ewers,Michael Ewers,Cathal Walsh,John Q. Trojanowski,Leslie M. Shaw,Ronald C. Petersen,Clifford R. Jack,Howard Feldman,Arun L.W. Bokde,Gene E. Alexander,Philip Scheltens,Bruno Vellas,Bruno Dubois,Michael W. Weiner,Michael W. Weiner,Harald Hampel +15 more
TL;DR: Short-term conversion to AD is predicted by single marker models to a comparable degree as by multimarker models in amnestic MCI subjects.
References
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The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the Road to Therapeutics
John Hardy,Dennis J. Selkoe +1 more
TL;DR: It has been more than 10 years since it was first proposed that the neurodegeneration in Alzheimer's disease (AD) may be caused by deposition of amyloid β-peptide in plaques in brain tissue and the rest of the disease process is proposed to result from an imbalance between Aβ production and Aβ clearance.
Journal ArticleDOI
Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease
TL;DR: The severity of dementia was positively related to the number of NFTs in neocortex, but not to the degree of SP deposition, and N FTs accumulate in a consistent pattern reflecting hierarchic vulnerability of individual cytoarchitectural fields.
Journal ArticleDOI
Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects.
Leslie M. Shaw,Hugo Vanderstichele,Malgorzata Knapik-Czajka,Christopher M. Clark,Paul S. Aisen,Ronald C. Petersen,Kaj Blennow,Holly Soares,Adam J. Simon,Piotr Lewczuk,Robert A. Dean,Eric Siemers,William Z. Potter,Virginia M.-Y. Lee,John Q. Trojanowski +14 more
TL;DR: Develop a cerebrospinal fluid biomarker signature for mild Alzheimer's disease (AD) in Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects.
Journal ArticleDOI
Reducing Endogenous Tau Ameliorates Amyloid ß-Induced Deficits in an Alzheimer's Disease Mouse Model
Erik D. Roberson,Kimberly Scearce-Levie,Jorge J. Palop,Fengrong Yan,Irene H. Cheng,Tiffany Wu,Hilary Gerstein,Gui Qiu Yu,Lennart Mucke +8 more
TL;DR: Reducing endogenous tau levels prevented behavioral deficits in transgenic mice expressing human amyloid precursor protein, without altering their high Aβ levels, and protected both transgenic and nontransgenic mice against excitotoxicity.
Journal ArticleDOI
Dendritic Function of Tau Mediates Amyloid-β Toxicity in Alzheimer's Disease Mouse Models
Lars M. Ittner,Yazi D. Ke,Fabien Delerue,Mian Bi,Amadeus Gladbach,Janet van Eersel,Heidrun Wölfing,Billy Chieng,MacDonald J. Christie,Ian A. Napier,Anne Eckert,Matthias Staufenbiel,Edna C. Hardeman,Jürgen Götz +13 more
TL;DR: It is shown that tau, known as axonal protein, has a dendritic function in postsynaptic targeting of the Src kinase Fyn, a substrate of which is the NMDA receptor (NR), which uncouples NR-mediated excitotoxicity and hence mitigates Abeta toxicity.
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