title: N-Terminal Hypothesis for Alzheimer's Disease.
abstract: Although the amyloid (abeta peptide, Aβ) hypothesis is 25 years old, is the dominant model of Alzheimer's disease (AD) pathogenesis, and guides the development of potential treatments, it is still controversial. One possible reason is a lack of a mechanistic path from the cleavage products of the amyloid precursor protein (APP) such as soluble Aβ monomer and soluble molecular fragments to the deleterious effects on synaptic form and function. From a review of the recent literature and our own published work including aggregation kinetics and structural morphology, Aβ clearance, molecular simulations, long-term potentiation measurements with inhibition binding, and the binding of a commercial monoclonal antibody, aducanumab, we hypothesize that the N-terminal domains of neurotoxic Aβ oligomers are implicated in causing the disease.
authors.affiliation: Howard P. Isermann Department of Chemical and Biological Engineering and the Center for Biotechnology & Interdisciplinary Studies, Rensselaer Polytechnic Institute , Troy, New York 12180-3590, United States.
authors.forename: Brian
authors.initials: B
authors.lastname: Murray
authors.affiliation: Howard P. Isermann Department of Chemical and Biological Engineering and the Center for Biotechnology & Interdisciplinary Studies, Rensselaer Polytechnic Institute , Troy, New York 12180-3590, United States.
authors.forename: Bhanushee
authors.initials: B
authors.lastname: Sharma
authors.affiliation: Howard P. Isermann Department of Chemical and Biological Engineering and the Center for Biotechnology & Interdisciplinary Studies, Rensselaer Polytechnic Institute , Troy, New York 12180-3590, United States.
authors.forename: Georges
authors.identifier: 0000-0002-7314-422X
authors.initials: G
authors.lastname: Belfort
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments
keywords: Alzheimer’s disease; Aβ peptide; N-terminus; fragments; multivalent interactions