Early-onset Alzheimer's disease with a presenilin-1 mutation at the site corresponding to the Volga German presenilin-2 mutation.
We describe a new mutation causing Alzheimer's disease (AD) in presenilin-1 (N135D) that is at the homologous site to the presenilin 2 mutation (N141I) in Volga German kindreds. The phenotype of PS1 N135D is an early-onset (34-38 years) disease. The mutation forms part of, and extends, the alpha-helical array of mutations in transmembrane 2 of the presenilins and leads to the suggestion that disruption of this helical face is the molecular insult that leads to disease.
Crook
R
R
Department of Psychiatry, University of South Florida, Tampa, USA.
Ellis
R
R
Shanks
M
M
Thal
L J
LJ
Perez-Tur
J
J
Baker
M
M
Hutton
M
M
Haltia
T
T
Hardy
J
J
Galasko
D
D
D000328:Adult; D000544:Alzheimer Disease / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008957:Models, Genetic; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D053764:Presenilin-1; D017385:Sequence Homology
D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1