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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White matter and cognition: making the connection
TL;DR: Evidence from behavioral neurology thatwhite matter lesions regularly disturb cognition is presented, the role of white matter in the physiology of distributed neural networks is considered, the hypothesis that white matter dysfunction is relevant to neurodegenerative disorders, and emerging concepts regarding the prevention and treatment of cognitive dysfunction associated with white matter disorders are discussed.
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Diffusion tensor MRI as a biomarker in axonal and myelin damage
TL;DR: The potential application and outstanding issues on the use of diffusion tensor imaging directional diffusivity as a biomarker in axonal and myelin damage in neurological disorders will be reviewed.
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Sequential relationships between grey matter and white matter atrophy and brain metabolic abnormalities in early Alzheimer's disease.
Nicolas Villain,Marine Fouquet,Jean-Claude Baron,Florence Mézenge,Brigitte Landeau,Vincent de la Sayette,Fausto Viader,Francis Eustache,Béatrice Desgranges,Gaël Chételat +9 more
TL;DR: The present study reinforces the relevance of remote mechanisms above local interactions to account for the pattern of metabolic brain alteration observed in amnestic mild cognitive impairment, and provides new avenues to assess the sequence of events in complex diseases characterized by multiple manifestations.
Journal ArticleDOI
Risk factors for Alzheimer's disease.
TL;DR: Risk factors may act collectively to cause AD pathology by promoting the liberation of oxygen free radicals with age, via environmental stress acting on regulatory genes early and later in life, or by increasing the cumulative 'allostatic load' on the body over a lifetime.
Book ChapterDOI
Anatomy of the Prefrontal Cortex
TL;DR: An overview of connectivity of the prefrontal cortex, arguably the most richly connected of all cortical regions, opens the way to subsequent chapters, where connectivity is found to be the key to all its functions.
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.