Thal amyloid stages do not significantly impact the correlation between neuropathological change and cognition in the Alzheimer disease continuum

Alberto Serrano-Pozo, Jing Qian, Alona Muzikansky, Sarah E. Monsell, Thomas J. Montine, Matthew P. Frosch, Rebecca A. Betensky, Bradley T. Hyman

Research output: Contribution to journalArticlepeer-review

Abstract

The 2012 neuropathological criteria for the diagnosis of Alzheimer disease (AD) summarize the extent of AD neuropathological change with an ABC score, which is a composite of the Thal stage of amyloid deposition (A), the Braak stage of neurofibrillary tangles (NFTs) (B), and the CERAD neuritic plaque score (C). NFTs and neuritic plaques are well-established contributors to cognitive impairment, but whether the Thal amyloid stage independently predicts antemortem cognition remains unknown. We used the National Alzheimer's Coordinating Center autopsy data set to build adjacent-categories logit regression models with CDR-SOB and Mini-Mental State Examination (MMSE) scores as cognitive outcome variables. Increasing CERAD scores were independently associated with higher CDR-SOB scores, whereas increasing Braak NFT stages predicted both higher CDR-SOB and lower MMSE scores. Increasing Thal amyloid stages were not significantly independently associated with either outcome measure. Increasing ABC scores predicted higher CDR-SOB and lower MMSE scores. These results raise the possibility that Thal amyloid stages do not substantially contribute to predicting antemortem cognition compared to CERAD neuritic plaque scores and Braak NFT stages, and suggest that the diffuse amyloid deposits participating in the assignment of Thal amyloid stages are neutral with respect to clinically detectable cognitive and functional changes.

Original languageEnglish (US)
Pages (from-to)516-526
Number of pages11
JournalJournal of Neuropathology and Experimental Neurology
Volume75
Issue number6
DOIs
StatePublished - Jun 1 2016

Keywords

  • ABC score
  • Alzheimer disease
  • Amyloid plaques
  • National Alzheimer's coordinating center
  • Neuritic plaques
  • Neurofibrillary tangles
  • Thal stages

ASJC Scopus subject areas

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

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