Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Defining the genetic architecture of Alzheimer's Disease: where next

Sims, Rebecca ORCID: https://orcid.org/0000-0002-3885-1199 and Williams, Julie ORCID: https://orcid.org/0000-0002-4069-0259 2016. Defining the genetic architecture of Alzheimer's Disease: where next. Neurodegenerative Diseases 16 (1-2) 10.1159/000440841

Full text not available from this repository.

Abstract

Background: Late-onset Alzheimer's disease is a genetically complex disorder. For 17 years, APOE was the only known susceptibility gene for disease. Through mostly genome-wide association studies, 25 loci are now known to associate with late-onset Alzheimer's disease. These susceptibility loci are not randomly distributed with respect to their functions. In fact, pathway analysis implicates significant enrichment of immunity, endocytosis, cholesterol metabolism, and ubiquitination in disease. Summary: Twenty-five loci have now been reliably shown to associate with Alzheimer's disease. However, a significant proportion of genetic variation in disease pathology is yet to be detected. Rare variation is being investigated through exome chip and next-generation sequencing experiments, which have already identified new protective and risk variants. Using a polygenic risk score approach, it is now possible to identify population groups with the greatest and fewest biological susceptibilities to disease. This method has proved more effective in predicting disease status than individual, genome-wide significant variants of small/moderate effect. Future studies will establish the specific functional changes that contribute to disease by piloting novel cellular modelling techniques using reprogrammed induced pluripotent stem cells from individuals with selected risk profiles. This will allow a variety of models to be produced to help understand disease mechanisms and test new drug therapies. Key Messages: Alzheimer's disease is a polygenic trait that has been linked to deficits in immunity, endocytosis, cholesterol metabolism and ubiquitination. Future work will focus on identifying rare disease susceptibility loci, unpicking the functional significance of the known risk loci and piloting novel cellular modelling techniques.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher: Karger A.C.
ISSN: 1660-2854
Date of Acceptance: 3 September 2015
Last Modified: 31 Oct 2022 10:21
URI: https://orca.cardiff.ac.uk/id/eprint/84493

Citation Data

Cited 11 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item