• Rebecca Koncz, Anbupalam Thalamuthu, Wei Wen, Vibeke S Catts, Vincent Dore, Teresa Lee, Karen A Mather, Melissa J Slavin, Eva A Wegner, Jiyang Jiang, Julian N Trollor, David Ames, Victor L Villemagne, Christopher C Rowe, Perminder S Sachdev, and Older Australian Twins Study collaborative team.
• Centre for Healthy Brain Ageing, School of Psychiatry, UNSW Sydney, Sydney, New South Wales, Australia r.koncz@unsw.edu.au.
• J. Neurol. Neurosurg. Psychiatr. 2022 Mar 1; 93 (3): 303-308.

ObjectiveTo determine the proportional genetic contribution to the variability of cerebral β-amyloid load in older adults using the classic twin design.MethodsParticipants (n=206) comprising 61 monozygotic (MZ) twin pairs (68 (55.74%) females; mean age (SD): 71.98 (6.43) years), and 42 dizygotic (DZ) twin pairs (56 (66.67%) females; mean age: 71.14 (5.15) years) were drawn from the Older Australian Twins Study. Participants underwent detailed clinical and neuropsychological evaluations, as well as MRI, diffusion tensor imaging (DTI) and amyloid PET scans. Fifty-eight participants (17 MZ pairs, 12 DZ pairs) had PET scans with 11Carbon-Pittsburgh Compound B, and 148 participants (44 MZ pairs, 30 DZ pairs) with 18Fluorine-NAV4694. Cortical amyloid burden was quantified using the centiloid scale globally, as well as the standardised uptake value ratio (SUVR) globally and in specific brain regions. Small vessel disease (SVD) was quantified using total white matter hyperintensity volume on MRI, and peak width of skeletonised mean diffusivity on DTI. Heritability (h 2) and genetic correlations were measured with structural equation modelling under the best fit model, controlling for age, sex, tracer and scanner.ResultsThe heritability of global amyloid burden was moderate (0.41 using SUVR; 0.52 using the centiloid scale) and ranged from 0.20 to 0.54 across different brain regions. There were no significant genetic or environmental correlations between global amyloid burden and markers of SVD.ConclusionAmyloid deposition, the hallmark early feature of Alzheimer's disease, is under moderate genetic influence, suggesting a major environmental contribution that may be amenable to intervention.© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.

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