Alzheimer's disease as homeostatic responses to age-related myelin breakdown
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This work delineates empirically testable mechanisms of action for genes underlying FAD and LOAD and provides "upstream" treatment targets and reframes key observations such as axonal transport disruptions, formation of axonal swellings/sphenoids and neuritic plaques, and proteinaceous deposits as by-products of homeostatic myelin repair processes.Citations
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Clinically silent Alzheimer's and vascular pathologies influence brain networks supporting executive function in healthy older adults
Brian T. Gold,Christopher A. Brown,Jonathan G. Hakun,Leslie M. Shaw,John Q. Trojanowski,Charles D. Smith +5 more
TL;DR: The results suggest that clinically silent AD pathology is related to lower expression of a fronto-visual fC pattern supporting executive task performance, and suggest that AD pathology and WMHs appear to be linked with ineffective increases in frontal response in CN older adults.
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Mitophagy and iron: two actors sharing the stage in age-associated neuronal pathologies.
TL;DR: This review briefly introduces the aging process and summarizes molecular mechanisms regulating mitophagy and iron homeostasis, and provides an overview on how dysfunction of these two processes impact on aging and age-associated neurodegenerative disorders with a focus on Alzheimer's disease, Parkinson's disease and Amyotrophic Lateral Sclerosis.
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Comparison of neurodegenerative types using different brain MRI analysis metrics in older adults with normal cognition, mild cognitive impairment, and Alzheimer's dementia.
Myungwon Choi,Hyun Chul Youn,Daegyeom Kim,Suji Lee,Sang Il Suh,Joon Kyung Seong,Hyun Ghang Jeong,Cheol E. Han +7 more
TL;DR: CerAD total scores were more sensitive to early changes of cortical structures than MMSE scores, and Cortical thickness analysis may be preferable in assessing brain structural MRI changes during AD-related cognitive decline, whereas LGI analysis may have limited capability to reflect the cognitive decrease.
Posted ContentDOI
Cell type-specific histone acetylation profiling of Alzheimer’s Disease subjects and integration with genetics
Easwaran Ramamurthy,Gwyneth Welch,Jemmie Cheng,Yixin Yuan,Laura Gunsalus,David A. Bennett,Li-Huei Tsai,Andreas R. Pfenning +7 more
TL;DR: It is confirmed that single nucleotide polymorphisms associated with late onset AD (LOAD) prefer to reside in the microglial histone acetylome, which varies most strongly with age, and deregulation of known and novel pathways in AD is revealed.
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Ex vivo MRI transverse relaxation in community based older persons with and without Alzheimer's dementia.
Lei Yu,Robert J. Dawe,Aron S. Buchman,Patricia A. Boyle,Julie A. Schneider,Konstantinos Arfanakis,David A. Bennett +6 more
TL;DR: The profile of R2 alterations in post‐mortem brains of persons with clinical diagnosis of AD dementia is characterized and how the profile differs after accounting for neuropathologic indices is investigated.
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.
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Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families
Elizabeth H. Corder,Ann M. Saunders,Warren J. Strittmatter,Donald E. Schmechel,P. C. Gaskell,Gary W. Small,A. D. Roses,Jonathan L. Haines,Margaret A. Pericak-Vance +8 more
TL;DR: The APOE-epsilon 4 allele is associated with the common late onset familial and sporadic forms of Alzheimer9s disease (AD) in 42 families with late onset AD.
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Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment.
Robert D. Terry,Eliezer Masliah,David P. Salmon,Nelson Butters,Richard DeTeresa,Robert Hill,Lawrence A. Hansen,Robert Katzman +7 more
TL;DR: Both linear regressions and multivariate analyses correlating three global neuropsychological tests with a number of structural and neurochemical measurements performed on a prospective series of patients with Alzheimer's disease and 9 neuropathologically normal subjects reveal very powerful correlations with all three psychological assays.
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Alzheimer's Disease Is a Synaptic Failure
TL;DR: Mounting evidence suggests that this syndrome begins with subtle alterations of hippocampal synaptic efficacy prior to frank neuronal degeneration, and that the synaptic dysfunction is caused by diffusible oligomeric assemblies of the amyloid β protein.
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Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory.
Ganesh M. Shankar,Shaomin Li,Tapan Mehta,Amaya Garcia-Munoz,Nina E. Shepardson,Imelda M. Smith,Francesca Brett,Michael A. Farrell,Michael J. Rowan,Cynthia A. Lemere,Ciaran M. Regan,Dominic M. Walsh,Bernardo L. Sabatini,Dennis J. Selkoe +13 more
TL;DR: It is concluded that soluble Aβ oligomers extracted from Alzheimer's disease brains potently impair synapse structure and function and that dimers are the smallest synaptotoxic species.