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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Could Iron Accumulation Be an Etiology of the White Matter Change in Alzheimer’s Disease: Using Phase Imaging to Detect White Matter Iron Deposition Based on Diffusion Tensor Imaging
TL;DR: Iron accumulation of Fx and PC regions was significantly positively correlated with FA value, indicating that abnormal iron deposition may be one of the causes of white matter disruption in AD.
Journal ArticleDOI
Association between changes in brain microstructure and cognition in older subjects at increased risk for vascular disease
Michiel Sala,Albert de Roos,Gerard J. Blauw,Huub A. M. Middelkoop,J. Wouter Jukema,Simon P. Mooijaart,Mark A. van Buchem,Anton J. M. de Craen,Jeroen van der Grond +8 more
TL;DR: MTR peak height is associated with cognitive function in older subjects at increased risk for vascular disease and has been found to be associated with performance on the STROOP test and delayed PWL test.
Dissertation
The influence of life course vascular risk on brain pathologies and cognition in later life - a neuroimaging study of the British 1946 birth cohort
TL;DR: Findings show that vascular risk factors influence late-life dementia risk through cerebral SVD and brain atrophy, and reinforce the importance of vascular risk management, starting at least in midlife, for reducing late- life dementia risk.
Posted ContentDOI
Metacognitive ability predicts hippocampal and prefrontal microstructure
Micah Allen,James C. Glen,Daniel Müllensiefen,Dietrich Samuel Schwarzkopf,Martina F. Callaghan,Geraint Rees +5 more
TL;DR: It is found that metacognitive ability, as determined by a signal-detection theoretic model, was positively related to the myelination, macromolecular and iron content of aPFC grey matter, suggesting metacognition depends upon the development and integrity of a memory-related brain network, potentially revealing novel biomarkers of neurodegeneration.
Journal ArticleDOI
Quantitative Magnetization Transfer of White Matter Tracts Correlates with Diffusion Tensor Imaging Indices in Predicting the Conversion from Mild Cognitive Impairment to Alzheimer's Disease.
Elena Makovac,Laura Serra,Carlotta Di Domenico,Camillo Marra,Carlo Caltagirone,Mara Cercignani,Marco Bozzali +6 more
TL;DR: Probabilistic white matter tractography results confirm the involvement of WM and particularly of association fibers in the progression of AD, highlighting disconnection as a potential mechanism.
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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.