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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.

Background: Only one study has investigated the relationship between cerebral β-amyloid (Aβ), apolipoprotein E (APOE) ε4 genotype, and cognition. Although significant relationships between cerebral Aβ and cognition were observed in ε4 carriers but not noncarriers, the magnitude of this relationship was not reported. Further, when demographic variables were controlled, the influence of APOE ε4 on the relationship between cerebral Aβ and cognition dissipated., Methods: In 144 healthy older adults who had undergone amyloid scanning and APOE ε4 genotyping in the Australian Imaging, Biomarkers, and Lifestyle (AIBL) Flagship Study of Ageing, correlations were conducted to determine the magnitude of relationship between cerebral Aβ and cognition in ε4 carriers and noncarriers. Fisher's Z was used to compare these correlations and Cohen's q determined the magnitude of difference between correlations., Results: Cerebral Aβ was significantly associated with tasks of visual and verbal episodic memory in APOE ε4 carriers. This association was not observed in ε4 noncarriers. The relationship between cerebral Aβ and episodic memory in ε4 carriers was significantly different from that in ε4 noncarriers, and the magnitude of this difference was small to moderate., Conclusions: In APOE ε 4 carriers, there is a moderate negative relationship between cerebral Aβ and episodic memory. This suggests that increased cerebral Aβ may signify the onset of preclinical AD, especially in healthy older adults who are genetically at risk for AD., (Copyright © 2013 The Alzheimer's Association. All rights reserved.)