Genetically identical twins show comparable tau PET load and spatial distribution

Emma M. Coomans, Jori Tomassen, Rik Ossenkoppele, Sandeep S. V. Golla, Marijke Den Hollander, Lyduine E. Collij, Emma Weltings, Sophie Van Der Landen, Emma E. Wolters, Albert D. Windhorst, Frederik Barkhof, Eco J.C. de Geus, Philip Scheltens, Pieter Jelle Visser, Bart N. M. Van Berckel, Anouk den Braber

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Tau accumulation starts during the preclinical phase of Alzheimer’s disease and is closely associated with cognitive decline. For preventive purposes, it is important to identify factors associated with tau accumulation and spread. Studying genetically identical twin-pairs may give insight into genetic and environmental contributions to tau pathology, as similarities in identical twin-pairs largely result from genetic factors, while differences in identical twin-pairs can largely be attributed to non-shared, environmental factors. This study aimed to examine similarities and dissimilarities in a cohort of genetically identical older twin-pairs in (i) tau load; and (ii) spatial distribution of tau, measured with 18F-flortaucipir PET.

We selected 78 genetically identical twins (39 pairs; average age 73 ± 6 years), enriched for amyloid-β pathology and APOE ε4 carriership, who underwent dynamic 18F-flortaucipir PET. We extracted binding potentials (BPND) in entorhinal, temporal, widespread neocortical and global regions, and examined within-pair similarities in BPND using age and sex corrected intra-class correlations. Furthermore, we tested whether twin-pairs showed a more similar spatial 18F-flortaucipir distribution compared to non-twin pairs, and whether the participant’s co-twin could be identified solely based on the spatial 18F-flortaucipir distribution. Last, we explored whether environmental (e.g. physical activity, obesity) factors could explain observed differences in twins of a pair in 18F-flortaucipir BPND.

On visual inspection, Alzheimer’s disease-like 18F-flortaucipir PET patterns were observed, and although we mainly identified similarities in twin-pairs, some pairs showed strong dissimilarities. 18F-flortaucipir BPND was correlated in twins in the entorhinal (r = 0.40; P = 0.01), neocortical (r = 0.59; P < 0.01) and global (r = 0.56; P < 0.01) regions, but not in the temporal region (r = 0.20; P = 0.10). The 18F-flortaucipir distribution pattern was significantly more similar between twins of the same pair [mean r = 0.27; standard deviation (SD) = 0.09] than between non-twin pairings of participants (mean r = 0.01; SD = 0.10) (P < 0.01), also after correcting for proxies of off-target binding. Based on the spatial 18F-flortaucipir distribution, we could identify with an accuracy of 86% which twins belonged to the same pair. Finally, within-pair differences in 18F-flortaucipir BPND were associated with within-pair differences in depressive symptoms (0.37 < β < 0.56), physical activity (−0.41 < β < −0.42) and social activity (−0.32 < β < −0.36) (all P < 0.05).

Overall, identical twin-pairs were comparable in tau load and spatial distribution, highlighting the important role of genetic factors in the accumulation and spreading of tau pathology. Considering also the presence of dissimilarities in tau pathology in identical twin-pairs, our results additionally support a role for (potentially modifiable) environmental factors in the onset of Alzheimer’s disease pathological processes, which may be of interest for future prevention strategies.
Original languageEnglish
Pages (from-to)3571-3581
Number of pages11
JournalBrain
Volume145
Issue number10
Early online date12 Jan 2022
DOIs
Publication statusPublished - Oct 2022

Funding

This study was made possible by the EU/European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative Joint Undertaking (EMIF grant 115372), the Grand Prix of the Association for Research on Alzheimer Disease, Alzheimer Nederland and ZonMW. This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115952. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation program and EFPIA. This communication reflects the views of the authors and neither IMI nor the European Union and EFPIA are liable for any use that may be made of the information contained herein.

FundersFunder number
Association for Research on Alzheimer Disease
EU/European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative115372
European Federation of Pharmaceutical Industries and Associations
European Commission
ZonMw
Innovative Medicines Initiative115952
Alzheimer Nederland

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