Correlation of alzheimer disease neuropathologic changes with cognitive status: A review of the literature

Peter T. Nelson, Irina Alafuzoff, Eileen H. Bigio, Constantin Bouras, Heiko Braak, Nigel J. Cairns, Rudolph J. Castellani, Barbara J. Crain, Peter Davies, Kelly Del Tredici, Charles Duyckaerts, Matthew P. Frosch, Vahram Haroutunian, Patrick R. Hof, Christine M. Hulette, Bradley T. Hyman, Takeshi Iwatsubo, Kurt A. Jellinger, Gregory A. Jicha, Enikö KövariWalter A. Kukull, James B. Leverenz, Seth Love, Ian R. MacKenzie, David M. Mann, Eliezer Masliah, Ann C. McKee, Thomas J. Montine, John C. Morris, Julie A. Schneider, Joshua A. Sonnen, Dietmar R. Thal, John Q. Trojanowski, Juan C. Troncoso, Thomas Wisniewski, Randall L. Woltjer, Thomas G. Beach

Research output: Contribution to journalReview articlepeer-review

948 Scopus citations


Clinicopathologic correlation studies are critically important for the field of Alzheimer disease (AD) research. Studies on human subjects with autopsy confirmation entail numerous potential biases that affect both their general applicability and the validity of the correlations. Many sources of data variability can weaken the apparent correlation between cognitive status and AD neuropathologic changes. Indeed, most persons in advanced old age have significant non-AD brain lesions that may alter cognition independently of AD. Worldwide research efforts have evaluated thousands of human subjects to assess the causes of cognitive impairment in the elderly, and these studies have been interpreted in different ways. We review the literature focusing on the correlation of AD neuropathologic changes (i.e. β-amyloid plaques and neurofibrillary tangles) with cognitive impairment. We discuss the various patterns of brain changes that have been observed in elderly individuals to provide a perspective forunderstanding AD clinicopathologic correlation and conclude that evidence from many independent research centers strongly supports the existence of a specific disease, as defined by the presence of Aβ plaques and neurofibrillary tangles. Although Aβ plaques may play a key role in AD pathogenesis, the severity of cognitive impairment correlates best with the burden of neocortical neurofibrillary tangles.

Original languageEnglish (US)
Pages (from-to)362-381
Number of pages20
JournalJournal of neuropathology and experimental neurology
Issue number5
StatePublished - May 2012


  • Aging
  • Alzheimer disease
  • Amyloid
  • Dementia
  • Epidemiology
  • MAPT
  • Neurofibrillary tangles
  • Neuropathology

ASJC Scopus subject areas

  • General Medicine


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