Associations of Alzheimer's disease risk variants with gene expression, amyloidosis, tauopathy, and neurodegeneration.
Alzheimer’s Disease Neuroimaging Initiative
Alzheimers Res Ther
Springer Science and Business Media LLC
MetadataShow full item record
Tan, M., Yang, Y., Xu, W., Wang, H., Tan, L., Zuo, C., Dong, Q., et al. (2021). Associations of Alzheimer's disease risk variants with gene expression, amyloidosis, tauopathy, and neurodegeneration.. Alzheimers Res Ther, 13 (1), 15. https://doi.org/10.1186/s13195-020-00755-7
BACKGROUND: Genome-wide association studies have identified more than 30 Alzheimer's disease (AD) risk genes, although the detailed mechanism through which all these genes are associated with AD pathogenesis remains unknown. We comprehensively evaluate the roles of the variants in top 30 non-APOE AD risk genes, based on whether these variants were associated with altered mRNA transcript levels, as well as brain amyloidosis, tauopathy, and neurodegeneration. METHODS: Human brain gene expression data were obtained from the UK Brain Expression Consortium (UKBEC), while other data used in our study were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We examined the association of AD risk allele carrier status with the levels of gene expression in blood and brain regions and tested the association with brain amyloidosis, tauopathy, and neurodegeneration at baseline, using a multivariable linear regression model. Next, we analyzed the longitudinal effects of these variants on the change rates of pathology using a mixed effect model. RESULTS: Altogether, 27 variants were detected to be associated with the altered expression of 21 nearby genes in blood and brain regions. Eleven variants (especially novel variants in ADAM10, IGHV1-68, and SLC24A4/RIN3) were associated with brain amyloidosis, 7 variants (especially in INPP5D, PTK2B) with brain tauopathy, and 8 variants (especially in ECHDC3, HS3ST1) with brain neurodegeneration. Variants in ADAMTS1, BZRAP1-AS1, CELF1, CD2AP, and SLC24A4/RIN3 participated in more than one cerebral pathological process. CONCLUSIONS: Genetic variants might play functional roles and suggest potential mechanisms in AD pathogenesis, which opens doors to uncover novel targets for AD treatment.
Alzheimer disease, Amyloid, Gene expression, Neurodegeneration, Risk variants, Tau, Alzheimer Disease, Amyloidosis, Gene Expression, Genome-Wide Association Study, Humans, Tauopathies
External DOI: https://doi.org/10.1186/s13195-020-00755-7
This record's URL: https://www.repository.cam.ac.uk/handle/1810/318751
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/
Recommended or similar items
The current recommendation prototype on the Apollo Repository will be turned off on 03 February 2023. Although the pilot has been fruitful for both parties, the service provider IKVA is focusing on horizon scanning products and so the recommender service can no longer be supported. We recognise the importance of recommender services in supporting research discovery and are evaluating offerings from other service providers. If you would like to offer feedback on this decision please contact us on: email@example.com