Pathways to Alzheimer's disease

• Published in: Journal of internal medicine Vol. 275; no. 3; pp. 296 - 303
• Main Authors: Hardy, J., Bogdanovic, N., Winblad, B., Portelius, E., Andreasen, N., Cedazo‐Minguez, A., Zetterberg, H.
• Format: Journal Article
• Language: English
• Published: England 01-03-2014
• Subjects: Alzheimer disease; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid; Amyloid - genetics; Amyloid - metabolism; Amyloid beta-Peptides; Amyloid beta-Peptides - antagonists & inhibitors; amyloid precursor protein; apolipoprotein E; avagacestat; bapineuzumab; Brain; Brain - metabolism; Cell biology; cellular distribution; cerebrospinal fluid level; cholesterol metabolism; cholesterol synthesis; cholesterol transport; clinical pathway; clusterin; complement classical pathway; drug clearance; Early Medical Intervention; follow up; gamma secretase inhibitor; genetic analysis; genetic association; Genetic Predisposition to Disease; genetic variability; Genetics; Humans; immunoglobulin G1 antibody; Immunotherapy; Immunotherapy - methods; innate immunity; Medicin och hälsovetenskap; Neurosciences; Neurovetenskaper; nonhuman; Notch3 receptor; pathogenesis; phase 1 clinical trial (topic); phase 2 clinical trial (topic); phase 3 clinical trial (topic); presenilin; priority journal; randomized controlled trial (topic); risk factor; semagacestat; signal transduction; solanezumab; Tau
• ISSN: 0954-6820; 1365-2796; 1365-2796
• DOI: 10.1111/joim.12192

Recent trials of anti‐amyloid agents have not produced convincing improvements in clinical outcome in Alzheimer's disease; however, the reason for these poor or inconclusive results remains unclear. Recent genetic data continue to support the amyloid hypothesis of Alzheimer's disease with protective variants being found in the amyloid gene and both common low‐risk and rare high‐risk variants for disease being discovered in genes that are part of the amyloid response pathways. These data support the view that genetic variability in how the brain responds to amyloid deposition is a potential therapeutic target for the disease, and are consistent with the notion that anti‐amyloid therapies should be initiated early in the disease process.