title: Mutation analysis of sporadic early-onset Alzheimer's disease using the NeuroX array.
abstract: We have screened sporadic early-onset Alzheimer's disease (sEOAD, n = 408) samples using the NeuroX array for known causative and predicted pathogenic variants in 16 genes linked to familial forms of neurodegeneration. We found 2 sEOAD individuals harboring a known causative variant in PARK2 known to cause early-onset Parkinson's disease; p.T240M (n = 1) and p.Q34fs delAG (n = 1). In addition, we identified 3 sEOAD individuals harboring a predicted pathogenic variant in MAPT (p.A469T), which has previously been associated with AD. It is currently unknown if these variants affect susceptibility to sEOAD, further studies would be needed to establish this. This work highlights the need to screen sEOAD individuals for variants that are more classically attributed to other forms of neurodegeneration.
authors: School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK. Electronic address: imelda.barber@psych.ox.ac.uk.
authors: Imelda S
authors: IS
authors: Barber
authors: School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK.
authors: Anne
authors: A
authors: Braae
authors: School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK.
authors: Naomi
authors: N
authors: Clement
authors: School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK.
authors: Tulsi
authors: T
authors: Patel
authors: School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK.
authors: Tamar
authors: T
authors: Guetta-Baranes
authors: School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK.
authors: Keeley
authors: K
authors: Brookes
authors: School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK.
authors: Christopher
authors: C
authors: Medway
authors: School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK.
authors: Sally
authors: S
authors: Chappell
authors: Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
authors: Rita
authors: R
authors: Guerreiro
authors: Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
authors: Jose
authors: J
authors: Bras
authors: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors: Dena
authors: D
authors: Hernandez
authors: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors: Andrew
authors: A
authors: Singleton
authors: Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
authors: John
authors: J
authors: Hardy
authors: Faculty of Medical and Human Sciences, Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, UK.
authors: David M
authors: DM
authors: Mann
authors: School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK.
authors: Kevin
authors: K
authors: Morgan
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010300:Parkinson Disease / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D016875:tau Proteins / Q000235:genetics
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein
keywords: Alzheimer's disease; Early-onset; NeuroX; Parkinson's disease; Screening; Sporadic