Neuropathology and cognitive impairment in alzheimer disease: A complex but coherent relationship

Peter T. Nelson, Heiko Braak, William R. Markesbery

Research output: Contribution to journalReview articlepeer-review

480 Scopus citations

Abstract

Amyloid plaques and neurofibrillary tangles (NFTs) are the pathological hallmarks of Alzheimer disease (AD). There is controversy regarding the use of current diagnostic criteria for AD and whether amyloid plaques and NFTs contribute to cognitive impairment. Because AD is specific to humans, rigorous and comprehensiveclinicopathologic studies are necessary to test and refine hypotheses of AD diagnosis and pathogenesis. Neither the clinical nor the pathological aspects of AD evolve in a linear manner, but thepredictable sequence of AD pathology allows for stage-based correlations with cognitive deterioration. We discuss subsets of patients with clinical dementia who lack amyloid plaques and NFTs and, conversely, whether individuals without antemortem cognitive impairment can harbor severe AD-type pathological findings at autopsy. There are many medical, technical, and anatomical challenges to clinicopathologic studies in AD. For example, at least two thirds of persons older than 80 years have non-AD brain diseases that can effect on cognitive function. We argue that existing data strongly support the hypothesis that both amyloid plaques and NFTs contribute to cognitive impairment.

Original languageEnglish
Pages (from-to)1-14
Number of pages14
JournalJournal of Neuropathology and Experimental Neurology
Volume68
Issue number1
DOIs
StatePublished - Jan 2009

Keywords

  • Acetylcholine
  • Aging
  • Cognition
  • Lewy
  • Mini-mental state examination
  • Stroke
  • Tau

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Fingerprint

Dive into the research topics of 'Neuropathology and cognitive impairment in alzheimer disease: A complex but coherent relationship'. Together they form a unique fingerprint.

Cite this