title: Presenilin 1 intronic polymorphism is not associated with Alzheimer type neuropathological changes or sporadic Alzheimer's disease.
abstract: BACKGROUND
  A genetic association between the presenilin 1 (PS-1) intronic polymorphism and sporadic Alzheimer's disease has been a matter of controversy. Recent findings have suggested that the PS-1 polymorphism is not associated with Alzheimer's disease or amyloid beta-protein (Abeta) deposition in brains from patients with Alzheimer's disease.
  
  
  OBJECTIVE
  To elucidate the influence of the PS-1 polymorphism on Alzheimer type neuropathological changes and the development of Alzheimer's disease, the relation between the PS-1 polymorphism and quantitative severity of Alzheimer type neuropathological changes in the brains from patients with Alzheimer's disease and non-demented subjects was studied.
  
  
  METHODS
  The PS-1 and apolipoprotein E (ApoE) genotypes, were examined, together with the densities of the senile plaques, senile plaques with dystrophic neurites, and neurofibrillary tangles in the brains from 36 postmortem confirmed patients with sporadic Alzheimer's disease and 86 non-demented subjects. Association of the PS-1 polymorphism with sporadic Alzheimer's disease and ages at onset and duration of illness in Alzheimer's disease was also examined.
  
  
  RESULTS
  The PS-1 polymorphism was not associated with the senile plaques, senile plaques with dystrophic neurites, or neurofibrillary tangles in Alzheimer's disease or non-demented subjects. There was no association of the PS-1 intronic polymorphism with Alzheimer's disease, ages at onset, or durations of illness in Alzheimer's disease. The results remained nonsignificant even when the PS-1 genotype groups were divided into the subgroups with different ApoE epsilon4 status.
  
  
  CONCLUSIONS
  The PS-1 intronic polymorphism does not itself have a direct causal role in the formation of Alzheimer type neuropathological changes or in the development of sporadic Alzheimer's disease.
authors.affiliation: Department of Neurology, Tokyo Medical and Dental University, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Sodeyama
authors.forename: Y
authors.initials: Y
authors.lastname: Itoh
authors.forename: N
authors.initials: N
authors.lastname: Suematsu
authors.forename: M
authors.initials: M
authors.lastname: Matsushita
authors.forename: E
authors.initials: E
authors.lastname: Otomo
authors.forename: H
authors.initials: H
authors.lastname: Mizusawa
authors.forename: M
authors.initials: M
authors.lastname: Yamada
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D001057:Apolipoproteins E / Q000235:genetics; D001344:Autopsy; D016022:Case-Control Studies; D018450:Disease Progression; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D053764:Presenilin-1; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D001057:Apolipoproteins E; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1