Mild cognitive impairment and asymptomatic alzheimer disease subjects: Equivalent β-amyloid and tau loads with divergent cognitive outcomes

Diego Iacono, Susan M. Resnick, Richard O'Brien, Alan B. Zonderman, Yang An, Olga Pletnikova, Gay Rudow, Barbara Crain, Juan C. Troncoso

Research output: Contribution to journalArticle

Abstract

Older adults with intact cognition before death and substantial Alzheimer disease (AD) lesions at autopsy have been termed "asymptomatic AD subjects" (ASYMAD). We previously reported hypertrophy of neuronal cell bodies, nuclei, and nucleoli in the CA1 of the hippocampus (CA1), anterior cingulate gyrus, posterior cingulate gyrus, and primary visual cortex of ASYMAD versus age-matched Control and mild cognitive impairment (MCI) subjects. However, it was unclear whether the neuronal hypertrophy could be attributed to differences in the severity of AD pathology. Here, we performed quantitative analyses of the severity of β-amyloid (Aβ) and phosphorylated tau (tau) loads in the brains of ASYMAD, Control, MCI, and AD subjects (n = 15 per group) from the Baltimore Longitudinal Study of Aging. Tissue sections from CA1, anterior cingulate gyrus, posterior cingulate gyrus, and primary visual cortex were immunostained for Aβ and tau; the respective loads were assessed using unbiased stereology by measuring the fractional areas of immunoreactivity for each protein in each region. The ASYMAD and MCI groups did not differ in Aβ and tau loads. These data confirm that ASYMAD and MCI subjects have comparable loads of insoluble Aβ and tau in regions vulnerable to AD pathology despite divergent cognitive outcomes. These findings imply that cognitive impairment in AD may be caused or modulated by factors other than insoluble forms of Aβ and tau.

Original languageEnglish (US)
Pages (from-to)295-304
Number of pages10
JournalJournal of neuropathology and experimental neurology
Volume73
Issue number4
DOIs
StatePublished - Apr 2014

Keywords

  • Alzheimer disease
  • Immunoreactivity
  • Neuronal hypertrophy
  • Preserved cognition
  • Soluble A-amyloid
  • Tau

ASJC Scopus subject areas

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

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