Lack of association of presenilin-1 intron-8 polymorphism with neuropathological features of Alzheimer's disease.
Over 45 mutations within the coding region of presenilin-1 (PS-1) are associated with an autosomal dominant form of Alzheimer's disease. Recently allele 1 of a polymorphism within intron-8 was reported to be in disequilibrium with Alzheimer's disease in a group of patients with sporadic Alzheimer's disease. This association has been replicated in some, but not all, studies. To determine whether the PS-1 intronic polymorphism is overrepresented in Alzheimer's disease in an autopsy-proven series, and to examine whether allele 1 is associated with a specific neuropathological phenotype, polymerase chain reaction based technique was used to assess the genotype in 85 cases of Alzheimer's disease. The resulting genotypes were compared with age of onset, duration of illness, and quantitative neuropathological measures of Abeta(total), Abeta(1-40), Abeta(1-42), neurofibrillary tangle number and neuron number. The 1/1 genotype did not associate with any differences in the clinical or neuropathological phenotype. These data suggest that the PS-1 intron-8 polymorphism does not strongly impact the clinical or neuropathologic features of Alzheimer's disease.
Liao
A
A
Alzheimer's Research, Department of Neurology, Massachusetts General Hospital-East, 149 13th Street, Charlestown, MA 02129, USA.
Gómez-Isla
T
T
Clatworthy
A
A
Hyman
B T
BT
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D005260:Female; D005799:Genes, Dominant; D005838:Genotype; D006801:Humans; D007438:Introns; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D053764:Presenilin-1
D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1