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- PMID: 24880964
- UKPMCID: 24880964
- DOI: 10.1016/j.neurobiolaging.2014.04.026
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Exome sequencing identifies 2 novel presenilin 1 mutations (p.L166V and p.S230R) in British early-onset Alzheimer's disease.
Sassi, Celeste; Guerreiro, Rita; Gibbs, Raphael; Ding, Jinhui; Lupton, Michelle K; Troakes, Claire; Lunnon, Katie; Al-Sarraj, Safa; Brown, Kristelle S; Medway, Chirstopher; Lord, Jenny; Turton, James; Mann, David; Snowden, Julie; Neary, David; Harris, Jeniffer; Bras, Jose; ; Morgan, Kevin; Powell, John F; Singleton, Andrew; Hardy, John
Neurobiology of aging. 2014;35(10):2422.e13-6.
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Full-text held externally
- PMID: 24880964
- UKPMCID: 24880964
- DOI: 10.1016/j.neurobiolaging.2014.04.026
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).
Keyword(s)
APP; British cohort; Early-onset Alzheimer's disease; PSEN1; PSEN2
Bibliographic metadata
- Sassi, Celeste
- Guerreiro, Rita
- Gibbs, Raphael
- Ding, Jinhui
- Lupton, Michelle K
- Troakes, Claire
- Lunnon, Katie
- Al-Sarraj, Safa
- Brown, Kristelle S
- Medway, Chirstopher
- Lord, Jenny
- Turton, James
- Mann, David
- Snowden, Julie
- Neary, David
- Harris, Jeniffer
- Bras, Jose
- Morgan, Kevin
- Powell, John F
- Singleton, Andrew
- Hardy, John
- Passmore, Peter
- Craig, David
- Johnston, Janet
- McGuinness, Bernadette
- Todd, Stephen
- Heun, Reinhard
- Kölsch, Heike
- Kehoe, Patrick G
- Hooper, Nigel M
- Vardy, Emma R L C
- Mann, David M
- Pickering-Brown, Stuart
- Brown, Kristelle
- Lowe, James
- Morgan, Kevin
- Smith, A David
- Wilcock, Gordon
- Warden, Donald
- Holmes, Clive
- 089698, Wellcome Trust, United Kingdom
- G-1107, Parkinson's UK, United Kingdom
- G0701441, Medical Research Council, United Kingdom
- P50 AG016574, NIA NIH HHS, United States
- R01 AG18023, NIA NIH HHS, United States
- U01 AG006786, NIA NIH HHS, United States
- WT089698, Wellcome Trust, United Kingdom
- ZO1 AG000950-10, NIA NIH HHS, United States