Expression of INPP5D Isoforms in Human Brain: Impact of Alzheimer’s Disease Neuropathology and Genetics

Diana J. Zajac, James Simpson, Eric Zhang, Ishita Parikh, Steven Estus

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


The single nucleotide polymorphisms rs35349669 and rs10933431 within Inositol Polyphosphate-5-Phosphatase D (INPP5D) are strongly associated with Alzheimer’s Disease risk. To better understand INPP5D expression in the brain, we investigated INPP5D isoform expression as a function of rs35349669 and rs10933431, as well as Alzheimer’s disease neuropathology, by qPCR and isoform-specific primers. In addition, INPP5D allelic expression imbalance was evaluated relative to rs1141328 within exon 1. Expression of INPP5D isoforms associated with transcription start sites in exon 1 and intron 14 was increased in individuals with high Alzheimer’s disease neuropathology. In addition, a novel variant with 47bp lacking from exon 12 increased expression in Alzheimer’s Disease brains, accounting for 13% of total INPP5D expression, and was found to undergo nonsense-mediated decay. Although inter-individual variation obscured a possible polymorphism effect on INPP5D isoform expression as measured by qPCR, rs35349669 was associated with rs1141328 allelic expression imbalance, suggesting that rs35349669 is significantly associated with full-length INPP5D isoform expression. In summary, expression of INPP5D isoforms with start sites in exon 1 and intron 14 are increased in brains with high Alzheimer’s Disease neuropathology, a novel isoform lacking the phosphatase domain was significantly increased with the disease, and the polymorphism rs35349669 correlates with allele-specific full-length INPP5D expression.

Original languageEnglish
Article number763
Issue number3
StatePublished - Mar 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.


  • Alzheimer’s disease
  • INPP5D
  • SHIP1
  • allelic expression imbalance
  • genetics
  • microglia
  • next-generation sequencing
  • single nucleotide polymorphism

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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