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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Multimodal magnetic resonance imaging assessment of white matter aging trajectories over the lifespan of healthy individuals.
George Bartzokis,George Bartzokis,Po H. Lu,Panthea Heydari,Alexander Couvrette,Grace J. Lee,Greta Kalashyan,Frank Freeman,John Grinstead,Pablo Villablanca,J. Paul Finn,Jim Mintz,Jeffry R. Alger,Lori L. Altshuler +13 more
TL;DR: The data suggest that the healthy adult brain undergoes continual change driven by development and repair processes devoted to creating and maintaining synchronous function among neural networks on which optimal cognition and behavior depend.
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White matter integrity and vulnerability to Alzheimer's disease: preliminary findings and future directions.
TL;DR: The present review summarizes recent evidence suggesting that WM integrity declines are present in individuals at high AD-risk, prior to cognitive decline, and DTI holds promise as a method to aid identification of presymptomatic AD.
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Sub-regional hippocampal injury is associated with fornix degeneration in Alzheimer's disease
Dong Young Lee,Evan Fletcher,Owen Carmichael,Baljeet Singh,Dan M Mungas,Bruce R Reed,Oliver Martinez,Michael H. Buonocore,Maria Persianinova,Charles DeCarli +9 more
TL;DR: The region-specific association between fornix integrity and hippocampal neuronal death may provide in vivo evidence for degenerative white matter injury in AD: axonal pathology that is closely linked to neuronal injury.
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Dynamic changes in myelin aberrations and oligodendrocyte generation in chronic amyloidosis in mice and men.
Gwendolyn Behrendt,Kristin Baer,Annalisa Buffo,Maurice A. Curtis,Richard L.M. Faull,Mark I. Rees,Magdalena Götz,Leda Dimou +7 more
TL;DR: It is demonstrated that oligodendrocyte progenitors specifically react to amyloid plaque deposition in an AD‐related mouse model as well as in human AD pathology, although with distinct outcomes.
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Novel white matter tract integrity metrics sensitive to Alzheimer disease progression.
Els Fieremans,Andreana Benitez,Jens H. Jensen,Maria F. Falangola,Ali Tabesh,Rachael L. Deardorff,Maria Vittoria Spampinato,James Babb,Dmitry S. Novikov,Steven H. Ferris,Joseph A. Helpern +10 more
TL;DR: Findings have implications for the course and spatial progression of white matter degeneration in Alzheimer disease, suggest the mechanisms by which these changes occur, and demonstrate the viability of these white matter tract integrity metrics as potential neuroimaging biomarkers of the earliest stages of Alzheimer disease and disease progression.
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.