Neuronal hypertrophy in asymptomatic Alzheimer disease

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

Research output: Contribution to journalArticlepeer-review


The pathologic changes of Alzheimer disease (AD) evolve very gradually over decades before the disease becomes clinically manifest. Thus, it is not uncommon to find substantial numbers of Aβ plaques and neurofibrillary tangles in autopsy brains of older subjects with documented normal cognition, a state that we define as asymptomatic AD (ASYMAD). The goal of this study is to understand the morphometric substrate of ASYMAD subjects compared with mild cognitive impairment and definite AD cases. We used designed-based stereology to measure the volumes of neuronal cell bodies, nuclei, and nucleoli in 4 cerebral regions: anterior cingulate gyrus, posterior cingulate gyrus, primary visual cortex, and CA1 of hippocampus. We examined and compared autopsy brains from 4 groups (n = 15 each) of participants in the Baltimore Longitudinal Study of Aging: ASYMAD, mild cognitive impairment, AD, and age-matched controls. We found significant hypertrophy of the neuronal cell bodies, nuclei, and nucleoli of CA1 of hippocampus and anterior cingulate gyrus neurons in ASYMAD subjects compared with control and mild cognitive impairment cases. In the posterior cingulate gyrus and primary visual cortex, the hypertrophy was limited to the nuclei and nucleoli. The hypertrophy of cortical neurons and their nuclei and nucleoli in ASYMAD may represent an early reaction to the presence of neurotoxic Aβ or tau, or a compensatory mechanism that prevents the progression of the disease into dementia.

Original languageEnglish (US)
Pages (from-to)578-589
Number of pages12
JournalJournal of neuropathology and experimental neurology
Issue number6
StatePublished - Jun 2008


  • Alzheimer disease pathogenesis
  • Mild cognitive impairment
  • Neuronal resistance
  • Nuclear hypertrophy
  • Nucleolar hypertrophy
  • Tau
  • βAmyloid

ASJC Scopus subject areas

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

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