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

Imelda S. Barber, Jennyfer M. Garc??a-C??rdenas, Chidchanok Sakdapanichkul, Christopher Deacon, Gabriela Zapata Erazo, Rita Guerreiro, Jose Bras, Dena Hernandez, Andrew B Singleton, Tamar Guetta-Baranes, Anne Braae, Naomi Clement, Tulsi Patel, Keeley Brookes, Christopher Medway, Sally Chappell, David M. Mann, Peter Passmore, David Craig, Janet JohnstonBernadette McGuinness, Stephen Todd, Reinhard Heun, Heike Kolsch, Patrick G Kehoe, Emma R L C Vardy, Nigel M Hooper, Stuart Pickering-Brown, Julie Snowden, Anna Richardson, Matt Jones, David Neary, Jenny Harris, James Lowe, A David Smith, Gordon Wilcock, Donald Warden, Clive Holmes, K. Morgan

Research output: Chapter in Book/Report/Conference proceedingChapter

8 Citations (Scopus)


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.
Original languageEnglish
Title of host publicationNeurobiology of Aging
PublisherElsevier Inc.
ISBN (Print)1558-1497 (Electronic)\r0197-4580 (Linking)
Publication statusPublished - 01 Mar 2016

Publication series

NameNeurobiology of Aging


  • APP
  • Alzheimer's disease
  • Early-onset
  • Rs367709245
  • Screening
  • Sporadic

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