O5‐07‐06: THE HERITABILITY OF AMYLOID DEPOSITION AND ITS SHARED GENETIC BASIS WITH SMALL VESSEL DISEASE IN THE BRAINS OF OLDER PEOPLE

Cerebral small vessel disease (SVD) and Alzheimer's disease (AD) pathology, namely β-amyloid (Aβ), commonly co-occur. Whether or not they share a genetic basis is unknown. Using the classical twin design, this study aims to (1) determine the heritability of amyloid deposition in the brains of older people, and (2) examine the shared genetic basis between SVD and amyloid pathology across multiple imaging modalities. Participants (N=206; 62 monozygotic (MZ) pairs & 41 dizygotic (DZ) pairs; Table 1) were drawn from the Older Australian Twins Study1. 58 participants (17 MZ, 12 DZ pairs) had PET scans with C11-PiB and 148 participants (45 MZ pairs, 29 DZ pairs) had PET scans with 18F-NAV. Cortical amyloid burden was quantified globally and in regions of interest (ROI) using the standardized uptake value ratio (SUVR). Total white matter hyperintensity volume (WMHV) on magnetic resonance imaging and peak width of skeletonized mean diffusivity (PSMD) on diffusion tensor imaging were used as markers of SVD. Detailed neuropsychological and clinical evaluations, including the assessment of vascular risk factors, were also completed. Heritability (h2) and genetic correlations were measured under the best fit AE model, controlling for age, sex and scanner, using the OpenMx package. The heritability (h2) of global SUVR was moderate (0.43), and that for ROIs ranged from 0.18 to 0.54, after correcting for age, sex and scanner (Table 2). The mean global SUVR was significantly higher in APOE ε4 carriers (1.61) when compared to non-carriers (1.30) (p<.001). There were no significant genetic (A) or environmental (E) correlations between global SUVR and markers of SVD (Figure). The genetic correlation between WMHV and PSMD was significant (0.64; 95% CI 0.41, 0.82).