Screening exons 16 and 17 of the amyloid precursor protein gene in sporadic early-onset Alzheimer's disease

Neurobiol Aging. 2016 Mar;39:220.e1-7. doi: 10.1016/j.neurobiolaging.2015.12.011. Epub 2015 Dec 29.

Abstract

Early-onset Alzheimer's disease (EOAD) can be familial (FAD) or sporadic EOAD (sEOAD); both have a disease onset ≤65 years of age. A total of 451 sEOAD samples were screened for known causative mutations in exons 16 and 17 of the amyloid precursor protein (APP) gene. Four samples were shown to be heterozygous for 1 of 3 known causative mutations: p.A713T, p.V717I, and p.V717G; this highlights the importance of screening EOAD patients for causative mutations. Additionally, we document an intronic 6 base pair (bp) deletion located 83 bp downstream of exon 17 (rs367709245, IVS17 83-88delAAGTAT), which has a nonsignificantly increased minor allele frequency in our sEOAD cohort (0.006) compared to LOAD (0.002) and controls (0.002). To assess the effect of the 6-bp deletion on splicing, COS-7 and BE(2)-C cells were transfected with a minigene vector encompassing exon 17. There was no change in splicing of exon 17 from constructs containing either wild type or deletion inserts. Sequencing of cDNA generated from cerebellum and temporal cortex of a patient harboring the deletion found no evidence of transcripts with exon 17 removed.

Keywords: APP; Alzheimer's disease; Early-onset; Screening; Sporadic; rs367709245.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / genetics*
  • Amyloid beta-Protein Precursor / genetics*
  • Base Pairing / genetics
  • Cohort Studies
  • Exons / genetics*
  • Female
  • Gene Deletion
  • Gene Frequency
  • Genetic Association Studies*
  • Genetic Testing
  • Humans
  • Introns / genetics
  • Male
  • Middle Aged
  • Mutation*
  • Sequence Analysis, DNA

Substances

  • Amyloid beta-Protein Precursor