Loss-of-function (LoF) variants in the lipid transporter ABCA7 significantly increase the risk of Alzheimer’s disease (odds ratio ~2)[1], yet the pathogenic mechanisms and the neural cell types affected by these variants remain largely unknown. Here, we performed single-nuclear RNA sequencing of 36 human post-mortem samples from the prefrontal cortex of 12 ABCA7 LoF carriers and 24 matched non-carrier control individuals from the ROSMAP longitudinal cohort study[2].

[1] Steinberg, S., Stefansson, H., Jonsson, T. et al. Loss-of-function variants in ABCA7 confer risk of Alzheimer's disease. Nat Genet 47, 445–447 (2015). https://doi.org/10.1038/ng.3246

[2] Bennett DA, Buchman AS, Boyle PA, Barnes LL, Wilson RS, Schneider JA. Religious Orders Study and Rush Memory and Aging Project. J Alzheimers Dis. 2018;64(s1):S161-S189. doi: 10.3233/JAD-179939. PMID: 29865057; PMCID: PMC6380522.