Alzheimer's Disease Genetics and ABCA7 Splicing

Jared B. Vasquez, James F. Simpson, Ryan Harpole, Steven Estus

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Both common and rare polymorphisms within ABCA7 have been associated with Alzheimer's disease (AD). In particular, the rare AD associated polymorphism rs200538373 was associated with altered ABCA7 exon 41 splicing and an AD risk odds ratio of ∼1.9. To probe the role of this polymorphism in ABCA7 splicing, we used minigene studies and qPCR of human brain RNA. We report aberrant ABCA7 exon 41 splicing in the brain of a carrier of the rs200538373 minor C allele. Moreover, minigene studies show that rs200538373 acts as a robust functional variant in vitro. Lastly, although the ABCA7 isoform with an extended exon 41 is predicted to undergo nonsense mediated RNA decay, this was not supported by qPCR analyses, which showed relatively normal ABCA7 mRNA levels in the carrier of the rs200538373 minor C allele. In summary, rs200538373 is a functional polymorphism that alters ABCA7 exon 41 splicing without grossly altering the level of ABCA7 mRNA.

Original languageEnglish
Pages (from-to)633-641
Number of pages9
JournalJournal of Alzheimer's Disease
Issue number2
StatePublished - 2017

Bibliographical note

Funding Information:
The authors acknowledge the NIH (R01-AG045775) and the BrightFocus Foundation (A2014210S) for funding this work, as well as the University of Kentucky AD Center Neuropathology Core for tissue (P30-AG028383). The authors also acknowledge Elsevier Press for allowing data re-use to generate Fig. 3. The authors appreciate David Fardo, PhD, for statistical consulting.

Publisher Copyright:
© 2017-IOS Press and the authors. All rights reserved.


  • ABCA7
  • Alzheimer's disease
  • SNP
  • genetics
  • splicing

ASJC Scopus subject areas

  • Neuroscience (all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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