Sassi, C; Guerreiro, R; Gibbs, R; Ding, J; Lupton, MK; Troakes, C; Lunnon, K; ... Hardy, J; + view all Sassi, C; Guerreiro, R; Gibbs, R; Ding, J; Lupton, MK; Troakes, C; Lunnon, K; Al-Sarraj, S; Brown, KS; Medway, C; Lord, J; Turton, J; Mann, D; Snowden, J; Neary, D; Harris, J; Bras, J; ARUK Consortium, -; Morgan, K; Powell, JF; Singleton, A; Hardy, J; - view fewer (2014) Exome sequencing identifies 2 novel presenilin 1 mutations (p.L166V and p.S230R) in British early-onset Alzheimer's disease. Neurobiol Aging , 35 (10) 2422.e13-2422.e16. 10.1016/j.neurobiolaging.2014.04.026.

PDF 1-s2.0-S0197458014003285-main.pdf Download (169kB)

Abstract

Early-onset Alzheimer's disease (EOAD) represents 1%-2% of the Alzheimer's disease (AD) cases, and it is generally characterized by a positive family history and a rapidly progressive symptomatology. Rare coding and fully penetrant variants in amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are the only causative mutations reported for autosomal dominant AD. Thus, in this study we used exome sequencing data to rapidly screen rare coding variability in APP, PSEN1, and PSEN2, in a British cohort composed of 47 unrelated EOAD cases and 179 elderly controls, neuropathologically proven. We report 2 novel and likely pathogenic variants in PSEN1 (p.L166V and p.S230R). A comprehensive catalog of rare pathogenic variants in the AD Mendelian genes is pivotal for a premortem diagnosis of autosomal dominant EOAD and for the differential diagnosis with other early onset dementias such as frontotemporal dementia (FTD) and Creutzfeldt-Jakob disease (CJD).

Download activity - last month

Export as CSVJSONXML

Download activity - last 12 months

Export as JSONXMLCSV

Downloads by country - last 12 months

Export as JSONXMLCSV

Archive Staff Only

View Item