Validation of a priori candidate Alzheimer's disease SNPs with brain amyloid-beta deposition

Michael Vacher; Tenielle Porter; Victor L Villemagne; Lidija Milicic; Madeline Peretti; Christopher Fowler; Ralph Martins; Stephanie Rainey-Smith; David Ames; Colin L Masters; Christopher C Rowe; James D Doecke; Simon M Laws

doi:10.1038/s41598-019-53604-5

Validation of a priori candidate Alzheimer's disease SNPs with brain amyloid-beta deposition

Sci Rep. 2019 Nov 19;9(1):17069. doi: 10.1038/s41598-019-53604-5.

Authors

Michael Vacher¹, Tenielle Porter^{2

3}, Victor L Villemagne^{4

5

6}, Lidija Milicic², Madeline Peretti², Christopher Fowler⁵, Ralph Martins⁷, Stephanie Rainey-Smith⁷, David Ames⁸, Colin L Masters⁵, Christopher C Rowe^{4

6}, James D Doecke⁹, Simon M Laws^{2

3

10}

Affiliations

¹ CSIRO Health and Biosecurity, Australian e-Health Research Centre, Floreat, 6014, Western Australia, Australia. michael.vacher@csiro.au.
² Collaborative Genomics Group, Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, 6027, Western Australia, Australia.
³ Cooperative Research Centre for Mental Health, Carlton South, 3053, Victoria, Australia.
⁴ Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, 3084, Victoria, Australia.
⁵ The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, 3052, Victoria, Australia.
⁶ Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, 3084, Victoria, Australia.
⁷ Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, 6027, Western Australia, Australia.
⁸ National Ageing Research Institute, Parkville, 3052, Victoria, Australia.
⁹ CSIRO Health and Biosecurity, Australian e-Health Research Centre, Herston, 4029, Queensland, Australia.
¹⁰ School of Pharmacy and Biomedical Sciences, Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley, 6102, Western Australia, Australia.

Abstract

The accumulation of brain amyloid β (Aβ) is one of the main pathological hallmarks of Alzheimer's disease (AD). However, the role of brain amyloid deposition in the development of AD and the genetic variants associated with this process remain unclear. In this study, we sought to identify associations between Aβ deposition and an a priori evidence based set of 1610 genetic markers, genotyped from 505 unrelated individuals (258 Aβ+ and 247 Aβ-) enrolled in the Australian Imaging, Biomarker & Lifestyle (AIBL) study. We found statistically significant associations for 6 markers located within intronic regions of 6 genes, including AC103796.1-BDNF, PPP3R1, NGFR, KL, ABCA7 & CALHM1. Although functional studies are required to elucidate the role of these genes in the accumulation of Aβ and their potential implication in AD pathophysiology, our findings are consistent with results obtained in previous GWAS efforts.

Publication types

Research Support, Non-U.S. Gov't
Validation Study

MeSH terms

Aged
Alzheimer Disease / genetics*
Alzheimer Disease / pathology*
Amyloid beta-Peptides / analysis*
Apolipoproteins E / genetics
Australia
Biomarkers / analysis
Brain / pathology
Female
Genetic Association Studies
Humans
Male
Membrane Transport Proteins / genetics
Mitochondrial Precursor Protein Import Complex Proteins
Polymorphism, Single Nucleotide / genetics*

Substances

Amyloid beta-Peptides
Apolipoproteins E
Biomarkers
Membrane Transport Proteins
Mitochondrial Precursor Protein Import Complex Proteins
TOMM40 protein, human