title: Alzheimer and frontotemporal pathology in subsets of primary progressive aphasia.
abstract: OBJECTIVE
  To identify predictors of Alzheimer's disease (AD) versus frontotemporal lobar degeneration pathology in primary progressive aphasia (PPA), and determine whether the AD pathology is atypically distributed to fit the aphasic phenotype.
  
  
  METHODS
  Neuropsychological and neuropathological analyses of 23 consecutive PPA autopsies. All had qualitative determination of neurofibrillary tangle (NFT) density. Additional quantitation was done in four of the PPA/AD cases and four AD cases with the typical amnestic dementia of the Alzheimer type.
  
  
  RESULTS
  The sample contained mostly logopenic, agrammatic, and mixed forms of PPA. All six agrammatics had frontotemporal lobar degeneration (five of six with tauopathy). Seven of the 11 logopenics had AD. In logopenics, lower memory scores increased the probability of AD, but there were exceptions. The PPA/AD group showed predominance of entorhinal NFT typical of the amnestic dementia of the Alzheimer type. In the small subgroup examined quantitatively, neocortical NFTs were more numerous in the left hemisphere of PPA/AD. However, the asymmetry was low and inconsistent. Neuritic plaques did not display consistent asymmetry. Apolipoprotein E4, a major risk factor for typical AD, did not predict AD pathology in PPA.
  
  
  CONCLUSIONS
  Subtyping PPA helps to predict AD versus frontotemporal lobar degeneration pathology at the group level. However, our results and the literature also indicate that no clinical predictor is completely reliable in individual patients. The inconsistent concordance of NFT distribution with the asymmetric atrophy and the nonamnestic phenotype also raises the possibility that the AD markers encountered at autopsy in PPA may not always reflect the nature of the initiating neurodegenerative process.
authors.affiliation: Cognitive Neurology and Alzheimer's Disease Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. mmesulam@northwestern.edu
authors.forename: Marsel
authors.initials: M
authors.lastname: Mesulam
authors.forename: Alissa
authors.initials: A
authors.lastname: Wicklund
authors.forename: Nancy
authors.initials: N
authors.lastname: Johnson
authors.forename: Emily
authors.initials: E
authors.lastname: Rogalski
authors.forename: Gabriel C
authors.initials: GC
authors.lastname: Léger
authors.forename: Alfred
authors.initials: A
authors.lastname: Rademaker
authors.forename: Sandra
authors.initials: S
authors.lastname: Weintraub
authors.forename: Eileen H
authors.initials: EH
authors.lastname: Bigio
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D018888:Aphasia, Primary Progressive / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D001284:Atrophy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D015415:Biomarkers; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D003704:Dementia / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D003937:Diagnosis, Differential; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D016874:Neurofibrillary Tangles / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D010641:Phenotype
chemical_list: D015415:Biomarkers