Gunasekaran TI, Meena D, Lee AJ, Wu S, Dumitrescu L, Sperling R, Hohman TJ, AlzheimersDiseaseNeuroimagingInitiativeandtheA4Study, Huang J, Dehghan A, Tzoulaki I, Mayeux R, Vardarajan B. Genome-wide scan of Flortaucipir PET levels finds JARID2 associated with cerebral tau deposition. 2024 Oct 07 10.1101/2024.10.04.24314853 (version 2) medRxiv.
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Mayo Clinic - Rochester
It’s great to see additional studies investigating genetic and molecular associations with tau pathology. Particularly with how closely tau burden and topography may impact clinical presentations, a better understanding of underlying drivers could influence prognostication and treatment targeting. The PRC2 complex has indirectly arisen in previous AD studies which implicated REST. The combination of findings (genetic association and Mendelian ramdomization on plasma proteins) in this work could further point toward a role for PRC2 in tau pathology. Some caution is likely warranted in interpreting the results, as the sample size included in the GWAS was on the modest side in relation to recent multi-site work (e.g., Nho et al., 2023), and the variants identified were relatively lower in frequency. In addition, it is not known how the different clinical compositions of the included cohorts may have affected the results of the GWAS. Nevertheless, a helpful addition to the literature.
References:
Nho K, Risacher SL, Apostolova L, Bice PJ, Brosch J, Deardorff R, Faber K, Farlow MR, Foroud T, Gao S, Rosewood T, Kim JP, Nudelman K, Yu M, Aisen P, Sperling R, Hooli B, Shcherbinin S, Svaldi D, Jack CR, Jagust WJ, Landau S, Vasanthakumar A, Waring JF, Doré V, Laws SM, Masters CL, Porter T, Rowe CC, Villemagne VL, Dumitrescu L, Hohman TJ, Libby JB, Mormino E, Buckley RF, Johnson K, Yang HS, Petersen RC, Ramanan VK, Vemuri P, Cohen AD, Fan KH, Kamboh MI, Lopez OL, Bennett DA, Ali M, Benzinger T, Cruchaga C, Hobbs D, De Jager PL, Fujita M, Jadhav V, Lamb BT, Tsai AP, Castanho I, Mill J, Weiner MW, Alzheimer’s Disease Neuroimaging Initiative (ADNI), Alzheimer’s Disease Neuroimaging Initiative – Department of Defense, Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Study (A4 Study), Australian Imaging, Biomarker & Lifestyle Study (AIBL), Saykin AJ. Novel CYP1B1-RMDN2 Alzheimer's disease locus identified by genome-wide association analysis of cerebral tau deposition on PET. medRxiv. 2023 Mar 22; PubMed.
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