Genes, pathways and risk prediction in Alzheimer's disease.

Alzheimer Disease / genetics Amyloid beta-Peptides / metabolism Apolipoproteins E / genetics Brain / metabolism Epistasis, Genetic Genetic Predisposition to Disease Genome-Wide Association Study Humans Lipid Metabolism / genetics Presenilin-1 / genetics Presenilin-2 / genetics Risk Factors White People / genetics

Journal

Human molecular genetics

ISSN: 1460-2083

Titre abrégé: Hum Mol Genet

Pays: England

ID NLM: 9208958

Informations de publication

Date de publication:
21 11 2019

Historique:

received: 18 02 2019

revised: 18 06 2019

accepted: 04 07 2019

pubmed: 25 7 2019

medline: 26 6 2020

entrez: 24 7 2019

Statut: ppublish

Résumé

The failure of recent clinical trials in Alzheimer's disease has highlighted the need for the development of a more complete understanding of the pathogenesis of the disorder and also a belief that therapies may only work if given very early in the disease process before overt symptoms occur. The rare, early onset forms of the disease are all caused by mutations which make amyloid deposition a more likely event. Here we discuss the recent data showing that, in contrast, much of the risk of late onset disease is encoded by loci involved in lipid metabolism and/or encoded by microglia. We discuss these finding and suggest that amyloid induced membrane damage may be a key factor in disease and also review the evidence that genome wide genetic analysis can substantially help in the prediction of those individuals at high risk of disease in the general population.

Identifiants

DOI: 10.1093/hmg/ddz163 PMID: 31332445

pubmed: 31332445

pii: 5537030

doi: 10.1093/hmg/ddz163

doi:

Substances chimiques

Amyloid beta-Peptides 0

Apolipoproteins E 0

PSEN1 protein, human 0

PSEN2 protein, human 0

Presenilin-1 0

Presenilin-2 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Review

Langues

eng