Genetic and environmental influences on Alzheimer’s disease neuroimaging signatures

• Published in: Alzheimer's & dementia Vol. 17; no. S4
• Main Authors: Williams, McKenna E., Gillespie, Nathan A., Dale, Anders M., Elman, Jeremy A., Eyler, Lisa T., Fennema‐Notestine, Christine, Hagler, Donald J., McEvoy, Linda K., Neale, Michael C., Panizzon, Matthew S., Sanderson‐Cimino, Mark E., Franz, Carol E., Kremen, William S.
• Format: Journal Article
• Language: English
• Published: 01.12.2021
• ISSN: 1552-5260; 1552-5279
• DOI: 10.1002/alz.054708

Background Composite scores of MRI‐based brain morphometry, commonly termed ‘Alzheimer’s disease (AD) signatures,’ have demonstrated associations with AD symptom severity and progression to AD. Our group recently showed that two AD signatures, a cortical thickness/volume and mean diffusivity (MD) signature, aid prediction of progression to mild cognitive impairment among cognitively normal adults in their 50s. Genetic and environmental influences on these signatures, and whether the signatures capture unique AD‐related variance, remains unclear. Method Participants were from the Vietnam Era Twin Study of Aging (age=56.18, SD=2.61). Our previously published thickness/volume signature, a novel MD signature using the same regions and weights as the thickness/volume signature, and an MRI‐based measure of predicted brain age (ns=310‐502) were used in trivariate twin models to determine the relative influence of genetic and environmental factors on each phenotype. Correlations were examined to determine if the latent genetic and environmental influences overlap among the three phenotypes. Result Heritability estimates were similar for the signatures and predicted brain age (0.68‐0.71). Phenotypic correlations ranged from ‐0.47 to 0.27. Genetic correlations were: 0.33 [95% CI: 0.19,0.47] (thickness/volume signature and predicted brain age); ‐0.55 [95% CI: ‐0.66,‐0.42] (MD signature and predicted brain age); and ‐0.36 [95% CI: ‐0.51,‐0.20] (thickness/volume and MD signatures). Conclusion Both AD brain signatures are highly heritable. However, despite very similar heritability estimates among the three phenotypes, genetic correlations demonstrated that the two AD signatures are not redundant with each other or with a measure of predicted brain age. The results suggest that each AD signature captures some unique genetic variance, including genetic influences that are distinct from genetic influences on general brain aging.