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BACKGROUND Brain iron promotes oxidative damage and protein oligomerization that result in highly prevalent age-related proteinopathies such as Alzheimer's disease (AD), Parkinson's disease (PD), and Dementia with Lewy Bodies (DLB). Men are more likely to develop such diseases at earlier ages than women but brain iron levels increase with age in both(More)
BACKGROUND Postmortem and in vivo imaging data support the hypothesis that premature myelin breakdown and subsequent homeostatic remyelination attempts with increased oligodendrocyte and iron levels may contribute to Huntington's Disease (HD) pathogenesis and the symmetrical progress of neuronal loss from earlier-myelinating striatum to later-myelinating(More)
There are two distinct viewpoints on the association of the inheritance of apolipoprotein E (APOE) alleles and the age of onset distribution of Alzheimer's disease (AD): genetic and phenotypic expression. There have been multiple corroborations of the APOE-epsilon 4 association with Alzheimer's disease in populations around the world in clinic based studies(More)
The apolipoprotein E (apoE) type 4 allele (APOE4) is a susceptibility gene for late-onset familial and sporadic Alzheimer disease. ApoE is found in some neurofibrillary tangle-bearing neurons, one of the major pathologic hallmarks of the disease. Neurofibrillary tangles contain paired helical filaments formed from hyperphosphorylated microtubule-associated(More)
A genetic classification of Alzheimer disease(s) (AD) is presented. We describe a potential metabolic process in individuals who inherit apolipoprotein E-epsilon 4 (APOE4, gene; apoE4, protein) alleles, leading to increased risk and earlier age of onset of late-onset Alzheimer disease. Apolipoprotein E-epsilon 3 (apoE3) binds to tau protein, possibly(More)
The extracellular matrix protein laminin profoundly affects neuronal adhesion, spreading, differentiation, and growth by binding integrin-type cell surface receptors. Laminin binds other basement membrane components, including heparan sulfate proteoglycans. Apolipoprotein E (apoE) also binds basement membrane and heparan sulfate proteoglycans and(More)
The risk of Alzheimer's disease is determined, in part, by inheritance of specific alleles of ApoE. Isoform specific interactions of ApoE have been shown with the microtubule-associated protein tau, which forms the neurofibrillary tangle in this disease. Synthetic peptides representing each of the four microtubule-binding domains of tau more avidly bind(More)
BACKGROUND Age-related myelin breakdown is most evident in later-myelinating white matter (LMwm) brain regions. This process might degrade cognitive processing speed (CPS) underlying age-related cognitive decline and the predominance of age as a risk factor for Alzheimer's disease (AD). Apolipoprotein E (ApoE) 4 allele is the second most important AD risk(More)
Researchers who develop new home technologies using connected devices often want to conduct large-scale field studies in homes to evaluate their technology, but conducting such studies today is extremely challenging. Inspired by the success of PlanetLab, which enabled development and evaluation of global network services, we are developing a shared(More)
The apolipoprotein E type 4 allele is a susceptibility gene for late-onset Alzheimer's disease. Apolipoprotein E is found in neurons, some of which contain paired helical filaments made of the microtubule-associated protein tau. Previous studies have demonstrated that the apoE3 isoform, but not the apoE4 isoform, binds tau with high avidity. Because the(More)