TY  - JOUR
KW  - APP
KW  -  Alzheimer's disease
KW  -  Exome sequencing
KW  -  GRN
KW  -  MAPT
KW  -  Neurodegenerative dementia
KW  -  PRNP
KW  -  PSEN1
KW  -  PSEN2
KW  -  Aged
KW  -  Aged
KW  -  80 and over
KW  -  Alzheimer Disease
KW  -  Amyloid beta-Protein Precursor
KW  -  Cohort Studies
KW  -  Dementia
KW  -  Diagnosis
KW  -  Differential
KW  -  Female
KW  -  Genetic Association Studies
KW  -  Genetic Predisposition to Disease
KW  -  Genetic Testing
KW  -  Genetic Variation
KW  -  Humans
KW  -  Intercellular Signaling Peptides and Proteins
KW  -  Male
KW  -  Middle Aged
KW  -  Presenilin-1
KW  -  Presenilin-2
KW  -  Prions
KW  -  tau Proteins
ID  - discovery1437467
N2  - The overlapping clinical and neuropathologic features between late-onset apparently sporadic Alzheimer's disease (LOAD), familial Alzheimer's disease (FAD), and other neurodegenerative dementias (frontotemporal dementia, corticobasal degeneration, progressive supranuclear palsy, and Creutzfeldt-Jakob disease) raise the question of whether shared genetic risk factors may explain the similar phenotype among these disparate disorders. To investigate this intriguing hypothesis, we analyzed rare coding variability in 6 Mendelian dementia genes (APP, PSEN1, PSEN2, GRN, MAPT, and PRNP), in 141 LOAD patients and 179 elderly controls, neuropathologically proven, from the UK. In our cohort, 14 LOAD cases (10%) and 11 controls (6%) carry at least 1 rare variant in the genes studied. We report a novel variant in PSEN1 (p.I168T) and a rare variant in PSEN2 (p.A237V), absent in controls and both likely pathogenic. Our findings support previous studies, suggesting that (1) rare coding variability in PSEN1 and PSEN2 may influence the susceptibility for LOAD and (2) GRN, MAPT, and PRNP are not major contributors to LOAD. Thus, genetic screening is pivotal for the clinical differential diagnosis of these neurodegenerative dementias.
EP  - 2881.e6
AV  - public
Y1  - 2014/12//
TI  - Investigating the role of rare coding variability in Mendelian dementia genes (APP, PSEN1, PSEN2, GRN, MAPT, and PRNP) in late-onset Alzheimer's disease
A1  - Sassi, C
A1  - Guerreiro, R
A1  - Gibbs, R
A1  - Ding, J
A1  - Lupton, MK
A1  - Troakes, C
A1  - Al-Sarraj, S
A1  - Niblock, M
A1  - Gallo, JM
A1  - Adnan, J
A1  - Killick, R
A1  - Brown, KS
A1  - Medway, C
A1  - Lord, J
A1  - Turton, J
A1  - Bras, J
A1  - Alzheimer's Research UK Consortium
A1  - Morgan, K
A1  - Powell, JF
A1  - Singleton, A
A1  - Hardy, J
JF  - Neurobiology of Aging
SN  - 1558-1497
UR  - http://dx.doi.org/10.1016/j.neurobiolaging.2014.06.002
N1  - Copyright © 2014 Elsevier Inc. Article available under CC BY licence
IS  - 12
SP  - 2881.e1
VL  - 35
ER  -