title: Brain expression of presenilins in sporadic and early-onset, familial Alzheimer's disease.
abstract: BACKGROUND
  Mutations in the presenilin proteins cause early-onset, familial Alzheimer's disease (FAD).
  
  
  METHODS
  We characterized the cellular localization and endoproteolysis of presenilin 2 (PS2) and presenilin 1 (PS1) in brains from 25 individuals with presenilin-mutations causing FAD, as well as neurologically normal individuals and individuals with sporadic Alzheimer's disease (AD).
  
  
  RESULTS
  Amino-terminal antibodies to both presenilins predominantly decorated large neurons. Regional differences between the broad distributions of the two presenilins were greatest in the cerebellum, where most Purkinje cells showed high levels of only PS2 immunoreactivity. PS2 endoproteolysis in brain yielded multiple amino-terminal fragments similar in size to the PS1 amino-terminal fragments detected in brain. In addition, two different PS2 amino-terminal antibodies also detected a prominent 42 kDa band that may represent a novel PS2 form in human brain. Similar to PS1 findings, neither amino-terminal nor antiloop PS2 antibodies revealed substantial full-length PS2 in brain. Immunocytochemical examination of brains from individuals with the N141I PS2 mutation or eight different PS1 mutations, spanning the molecule from the second transmembrane domain to the large cytoplasmic loop domain, revealed immunodecoration of no senile plaques and only neurofibrillary tangles in the M139I PS1 mutation stained with PS1 antibodies.
  
  
  CONCLUSIONS
  Overall presenilin expression and the relative abundance of full-length and amino-terminal fragments in presenilin FAD cases were similar to control cases and sporadic AD cases. Thus, accumulation of full-length protein or other gross mismetabolism of neither PS2 nor PS1 is a consequence of the FAD mutations examined.
authors: Nathan Kline Institute, New York University School of Medicine, Organgeburg, New York 10962, USA. mathews@nki.rfmh.org
authors: P M
authors: PM
authors: Mathews
authors: A M
authors: AM
authors: Cataldo
authors: B H
authors: BH
authors: Kao
authors: A G
authors: AG
authors: Rudnicki
authors: X
authors: X
authors: Qin
authors: J L
authors: JL
authors: Yang
authors: Y
authors: Y
authors: Jiang
authors: M
authors: M
authors: Picciano
authors: C
authors: C
authors: Hulette
authors: C F
authors: CF
authors: Lippa
authors: T D
authors: TD
authors: Bird
authors: D
authors: D
authors: Nochlin
authors: J
authors: J
authors: Walter
authors: C
authors: C
authors: Haass
authors: L
authors: L
authors: Lévesque
authors: P E
authors: PE
authors: Fraser
authors: A
authors: A
authors: Andreadis
authors: R A
authors: RA
authors: Nixon
mesh_terms: D017668:Age of Onset; D000544:Alzheimer Disease / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D053764:Presenilin-1; D053766:Presenilin-2; D017386:Sequence Homology, Amino Acid
chemical_list: D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2