TY - JOUR
T1 - Neuronal hypertrophy in asymptomatic Alzheimer disease
AU - Iacono, Diego
AU - O'Brien, Richard
AU - Resnick, Susan M.
AU - Zonderman, Alan B.
AU - Pletnikova, Olga
AU - Rudow, Gay
AU - An, Yang
AU - West, Mark J.
AU - Crain, Barbara
AU - Troncoso, Juan C.
PY - 2008/6
Y1 - 2008/6
N2 - 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.
AB - 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.
KW - Alzheimer disease pathogenesis
KW - Mild cognitive impairment
KW - Neuronal resistance
KW - Nuclear hypertrophy
KW - Nucleolar hypertrophy
KW - Tau
KW - βAmyloid
UR - http://www.scopus.com/inward/record.url?scp=44649147170&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=44649147170&partnerID=8YFLogxK
U2 - 10.1097/NEN.0b013e3181772794
DO - 10.1097/NEN.0b013e3181772794
M3 - Article
C2 - 18520776
AN - SCOPUS:44649147170
SN - 0022-3069
VL - 67
SP - 578
EP - 589
JO - Journal of neuropathology and experimental neurology
JF - Journal of neuropathology and experimental neurology
IS - 6
ER -