title: Prefibrillar tau oligomers in mild cognitive impairment and Alzheimer's disease.
abstract: BACKGROUND
  Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of extracellular amyloid-β peptide and intracellular tau. Here, we review data suggesting that prefibrillar tau oligomers mediate cognitive decline early in the disease.
  
  
  OBJECTIVE
  It was our aim to study the presence of tau-positive pretangle neurons and correlate findings with cognitive test scores.
  
  
  METHODS
  Pretangle antibodies (TOC1 and pS422) were applied to tissue containing cholinergic basal forebrain neurons from people who died with a premortem clinical diagnosis of no cognitive impairment, mild cognitive impairment and AD.
  
  
  RESULTS
  Data lend support to the concept that tau oligomers are the toxic form of tau, that non-fibillar tau relates to cognitive dysfunction and that the earliest pretangle pathology occurs in neuritic processes.
  
  
  CONCLUSIONS
  Clinicopathological findings highlight the importance of studying tau modifications in neuronal soma and neuritic processes, which may be the earliest pathological lesions that correlate with cognitive status.
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, Ill., USA.
authors.forename: Elliott J
authors.initials: EJ
authors.lastname: Mufson
authors.forename: Sarah
authors.initials: S
authors.lastname: Ward
authors.forename: Lester
authors.initials: L
authors.lastname: Binder
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000378:metabolism / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D018613:Microscopy, Confocal; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D010446:Peptide Fragments; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D016875:tau Proteins
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