Protein misfolding disorders are associated with conformational changes in specific proteins, leading to the formation of potentially neurotoxic amyloid fibrils. During pathogenesis of prion disease, the prion protein misfolds into β-sheet rich, protease-resistant isoforms. A key, hydrophobic domain within the prion protein, comprising residues 109-122, recapitulates many properties of the full...

The understanding of the key mechanisms behind human brain deterioration in Alzheimer' disease (AD) is a highly active field of research. The most widespread hypothesis considers a cascade of events initiated by amyloid-β peptide fibrils that ultimately lead to the formation of the lethal amyloid plaques. Recent studies have shown that other agents, in particular magnetite, can also play a pivo...

PURPOSE OF REVIEW APOE4 genotype is the strongest genetic risk factor for Alzheimer's disease. Prevailing evidence suggests that amyloid β plays a critical role in Alzheimer's disease. The objective of this article is to review the recent findings about the metabolism of apolipoprotein E (ApoE) and amyloid β and other possible mechanisms by which ApoE contributes to the pathogenesis of Alzheime...

Inactivity, obesity, and insulin resistance are significant risk factors for the development of Alzheimer's disease (AD). Several studies have demonstrated that diet-induced obesity, inactivity, and insulin resistance exacerbate the neuropathological hallmarks of AD. The aggregation of β-amyloid peptides is one of these hallmarks. β-Site amyloid precursor protein-cleaving enzyme 1 (BACE1) is th...

Amyloid-β peptide (Aβ) oligomers are pathogenic species of amyloid aggregates in Alzheimer's disease. Like certain protein toxins, Aβ permeabilize cellular membranes, presumably through a pore formation mechanism. Owing to their structural and stoichiometric heterogeneity, the structure these pores remains be characterized. We studied functional Aβ42-pore equivalent, created by fusing Aβ42 olig...

Amyloidogenic peptides are well known for their involvement in diseases such as type 2 diabetes and Alzheimer's disease. However, more recently, amyloid fibrils have been shown to provide scaffolding and protection as functional materials in a range of organisms from bacteria to humans. These roles highlight the incredible tensile strength of the cross-β amyloid architecture. Many amino acid se...

Alzheimer’s disease (AD) is a neurodegenerative disorder and the leading cause of senile dementia. The brains of AD patients show two major pathological hallmarks: amyloid or senile plaques (SPs) and neurofibrillary tangles (NFTs). While NFTs are bundles of protein filaments found in the cytoplasm of neurons, SPs are extracellular aggregates of insoluble protein fibrils. The major component of ...

β-Amyloid (Aβ), a vasoactive protein, and elevated blood pressure (BP) levels are associated with Alzheimer disease (AD) and possibly vascular dementia. We investigated the joint association of midlife BP and Aβ peptide levels with the risk for late-life AD and vascular dementia. Subjects were 667 Japanese-American men (including 73 with a brain autopsy), from the prospective Honolulu Heart Pro...

Autoantibody catalyzed hydrolysis of amyloid β peptide* Hiroaki Taguchi Stephanie Planque, Yasuhiro Nishiyama, Jindrich Symersky, Stephane Boivin, Paul Szabo, Robert P. Friedland, Paul A. Ramsland, Allen B. Edmundson, Marc E. Weksler, Sudhir Paul Chemical Immunology Research Center, Univ of Texas Houston Medical School, Houston, TX 77030, USA; Weill Medical College of Cornell University, New Yo...