TY - JOUR
T1 - Clinical, imaging, pathological, and biochemical characterization of a novel presenilin 1 mutation (N135Y) causing Alzheimer's disease
AU - Natelson Love, Marissa
AU - Clark, David G.
AU - Cochran, J. Nicholas
AU - Den Beste, Kyle A.
AU - Geldmacher, David S.
AU - Benzinger, Tammie L.
AU - Gordon, Brian A.
AU - Morris, John C.
AU - Bateman, Randall J.
AU - Roberson, Erik D.
N1 - Publisher Copyright:
© 2016
PY - 2017/1/1
Y1 - 2017/1/1
N2 - We present 2 cases of early-onset Alzheimer's disease due to a novel N135Y mutation in PSEN1. The proband presented with memory and other cognitive symptoms at age 32. Detailed clinical characterization revealed initial deficits in memory with associated dysarthria, progressing to involve executive dysfunction, spastic gait, and episodic confusion with polyspike discharges on long-term electroencephalography. Amyloid- and FDG-PET scans showed typical results of Alzheimer's disease. By history, the proband's father had developed cognitive symptoms at age 42 and died at age 48. Neuropathological evaluation confirmed Alzheimer's disease, with moderate to severe amyloid angiopathy. Skeletal muscle showed type 2 fiber–predominant atrophy with pale central clearing. Genetic testing of the proband revealed an N135Y missense mutation in PSEN1. This mutation was predicted to be pathogenic by in silico analysis. Biochemical analysis confirmed that the mutation caused an increased Aβ42/Aβ40 ratio, consistent with other PSEN1 mutations and with a loss of presenilin function.
AB - We present 2 cases of early-onset Alzheimer's disease due to a novel N135Y mutation in PSEN1. The proband presented with memory and other cognitive symptoms at age 32. Detailed clinical characterization revealed initial deficits in memory with associated dysarthria, progressing to involve executive dysfunction, spastic gait, and episodic confusion with polyspike discharges on long-term electroencephalography. Amyloid- and FDG-PET scans showed typical results of Alzheimer's disease. By history, the proband's father had developed cognitive symptoms at age 42 and died at age 48. Neuropathological evaluation confirmed Alzheimer's disease, with moderate to severe amyloid angiopathy. Skeletal muscle showed type 2 fiber–predominant atrophy with pale central clearing. Genetic testing of the proband revealed an N135Y missense mutation in PSEN1. This mutation was predicted to be pathogenic by in silico analysis. Biochemical analysis confirmed that the mutation caused an increased Aβ42/Aβ40 ratio, consistent with other PSEN1 mutations and with a loss of presenilin function.
KW - Alzheimer's disease
KW - Elecrtoencephalography
KW - PET scan
KW - Presenilin 1
UR - http://www.scopus.com/inward/record.url?scp=85001907604&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2016.09.020
DO - 10.1016/j.neurobiolaging.2016.09.020
M3 - Article
C2 - 27793474
AN - SCOPUS:85001907604
SN - 0197-4580
VL - 49
SP - 216.e7
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -