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

Barber, Imelda S.; Garc�a-C�rdenas, Jennyfer M.; Sakdapanichkul, Chidchanok; Deacon, Christopher; Zapata Erazo, Gabriela; Guerreiro, Rita; Bras, Jose; Hernandez, Dena; Singleton, Andrew; Clement, Naomi; Guetta-Baranes, Tamar; Braae, Anne; Patel, Tulsi; Brookes, Keeley; Medway, Christopher; Chappell, Sally; Mann, David M.

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


Imelda S. Barber

Jennyfer M. Garc�a-C�rdenas

Chidchanok Sakdapanichkul

Christopher Deacon

Gabriela Zapata Erazo

Rita Guerreiro

Jose Bras

Dena Hernandez

Andrew Singleton

Naomi Clement

Tamar Guetta-Baranes

Anne Braae

Tulsi Patel

Keeley Brookes

Christopher Medway

Sally Chappell

David M. Mann


Early-onset Alzheimer’s disease (EOAD) can be familial (FAD) or sporadic (sEOAD); both have a disease onset ≤ 65 years of age. 451 sEOAD samples were screened for known causative mutations in exon 16 and 17 of the Amyloid Precursor Protein gene (APP). Four samples were shown to be heterozygous for one of three 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 harbouring the deletion found no evidence of transcripts with exon 17 removed.

Journal Article Type Article
Acceptance Date Dec 20, 2015
Online Publication Date Dec 29, 2015
Publication Date Mar 1, 2016
Deposit Date Feb 11, 2016
Publicly Available Date Feb 11, 2016
Journal Neurobiology of Aging
Print ISSN 0197-4580
Electronic ISSN 1558-1497
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 39
Pages 220.e1-220.e7
Keywords Alzheimer's disease, early-onset, sporadic, screening, APP, rs367709245
Public URL
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