title: AMY plaques in familial AD: comparison with sporadic Alzheimer's disease.
abstract: OBJECTIVE
  To assess AMY expression in familial AD (FAD).
  
  
  BACKGROUND
  The discovery of nonbeta-amyloid (Abeta), plaque-like deposits composed of a 100-kd protein (AMY) in sporadic AD (SAD) brains prompted us to determine whether these plaques (AMY plaques) also occur in AD due to mutations of the presenilin-1 (PS-1), presenilin-2 (PS-2), or the amyloid precursor protein (APP) genes.
  
  
  METHODS
  We used immunohistochemistry and confocal laser scanning microscopy to probe the brains of 22 patients with FAD (13 with PS-1, 5 with PS-2, and 4 with APP mutations) and 14 patients with SAD.
  
  
  RESULTS
  AMY plaques were present in all SAD and FAD brains, including an FAD/PS-1 brain from an individual with preclinical disease. The morphology of AMY plaques in SAD and FAD brains was indistinguishable, but they differed from Abeta deposits because AMY plaques lacked an immunoreactive core. AMY plaques sometimes colocalized with Abeta(x-42) deposits, but they did not colocalize with Abeta(x-40) plaque cores in either SAD or FAD brains. The percent of cortical area occupied by AMY was greater in FAD than in SAD brains (mean percent area = 9.8% and 5.9%, t = 2.487, p = 0.018). In particular, APP and PS-1 cases had more AMY deposition than PS-2 or SAD cases (12.9%, 10.5%, 6.2% in APP, PS-1, and PS-2 AD).
  
  
  CONCLUSIONS
  AMY plaques are consistently present in familial AD due to presenilin-1 (PS-1), PS-2, and amyloid precursor protein mutations, and they can begin to accumulate before the emergence of dementia.
authors.affiliation: Department of Neurology, MCP-Hahnemann University, Philadelphia, PA 19102, USA. lippa@auhs.edu
authors.forename: C F
authors.initials: CF
authors.lastname: Lippa
authors.forename: M L
authors.initials: ML
authors.lastname: Schmidt
authors.forename: L E
authors.initials: LE
authors.lastname: Nee
authors.forename: T
authors.initials: T
authors.lastname: Bird
authors.forename: D
authors.initials: D
authors.lastname: Nochlin
authors.forename: C
authors.initials: C
authors.lastname: Hulette
authors.forename: H
authors.initials: H
authors.lastname: Mori
authors.forename: V M
authors.initials: VM
authors.lastname: Lee
authors.forename: J Q
authors.initials: JQ
authors.lastname: Trojanowski
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D000682:Amyloid / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D001921:Brain / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D018613:Microscopy, Confocal; D008875:Middle Aged; D009154:Mutation; D010446:Peptide Fragments / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology*; D053764:Presenilin-1; D053766:Presenilin-2
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; D053766:Presenilin-2