title: Clinicopathological concordance and discordance in three monozygotic twin pairs with familial Alzheimer's disease.
abstract: OBJECTIVE
  Neuropathological examination of both individuals in a monozygotic (MZ) twin pair with Alzheimer's disease (AD) is rare, especially in the molecular genetic era. We had the opportunity to assess the concordance and discordance of clinical presentation and neuropathology in three MZ twin pairs with AD.
  
  
  METHODS
  The MZ twins were identified and characterised by the University of Washington Alzheimer's Disease Research Center. We reviewed the available clinical and neuropathological records for all six cases looking specifically for concordance and discordance of clinical phenotype, neuritic amyloid plaques (NP), neurofibrillary tangles (NFT) and Lewy related pathology (LRP).
  
  
  RESULTS
  Discordance in age of onset for developing AD in the MZ twins varied from 4 to 18 years. Clinical presentations also differed between twins. One twin presented with a dementia with Lewy Body clinical syndrome while the other presented with typical clinical AD. Neuropathology within the MZ twin pairs was concordant for NP and NFT, regardless of duration of disease, and was discordant for LRP. This difference was most marked in the late onset AD twin pair. One pair was found to have a mutation in presenilin-1 (PS1) (A79V) with remarkably late onset in a family member.
  
  
  CONCLUSIONS
  MZ twins with AD can vary considerably in age of onset, presentation and disease duration. The concordance of NP and NFT pathological change and the discordance of LRP support the concept that, in AD, the former are primarily under genetic control whereas the latter (LRP) is more influenced by disease duration and environmental factors. The A79V mutation in PS1 can be associated with very late onset of dementia.
authors.affiliation: Neurological Foundation of New Zealand, New Zealand.
authors.forename: Kiri L
authors.initials: KL
authors.lastname: Brickell
authors.forename: James B
authors.initials: JB
authors.lastname: Leverenz
authors.forename: Ellen J
authors.initials: EJ
authors.lastname: Steinbart
authors.forename: Malia
authors.initials: M
authors.lastname: Rumbaugh
authors.forename: Gerard D
authors.initials: GD
authors.lastname: Schellenberg
authors.forename: David
authors.initials: D
authors.lastname: Nochlin
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Lampe
authors.forename: Ida E
authors.initials: IE
authors.lastname: Holm
authors.forename: Vivianna
authors.initials: V
authors.lastname: Van Deerlin
authors.forename: Wuxing
authors.initials: W
authors.lastname: Yuan
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Bird
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D002544:Cerebral Infarction / Q000150:complications / Q000175:diagnosis; D018450:Disease Progression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016874:Neurofibrillary Tangles / Q000235:genetics / Q000473:pathology; D010300:Parkinson Disease / Q000150:complications; D010375:Pedigree; D058225:Plaque, Amyloid / Q000235:genetics / Q000473:pathology; D014430:Twins, Monozygotic / Q000235:genetics*