TY - JOUR
T1 - Mild cognitive impairment and asymptomatic alzheimer disease subjects
T2 - Equivalent β-amyloid and tau loads with divergent cognitive outcomes
AU - Iacono, Diego
AU - Resnick, Susan M.
AU - O'Brien, Richard
AU - Zonderman, Alan B.
AU - An, Yang
AU - Pletnikova, Olga
AU - Rudow, Gay
AU - Crain, Barbara
AU - Troncoso, Juan C.
PY - 2014/4
Y1 - 2014/4
N2 - 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.
AB - 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.
KW - Alzheimer disease
KW - Immunoreactivity
KW - Neuronal hypertrophy
KW - Preserved cognition
KW - Soluble A-amyloid
KW - Tau
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U2 - 10.1097/NEN.0000000000000052
DO - 10.1097/NEN.0000000000000052
M3 - Article
C2 - 24607960
AN - SCOPUS:84897418099
SN - 0022-3069
VL - 73
SP - 295
EP - 304
JO - Journal of neuropathology and experimental neurology
JF - Journal of neuropathology and experimental neurology
IS - 4
ER -