title: Mild cognitive impairment and asymptomatic Alzheimer disease subjects: equivalent β-amyloid and tau loads with divergent cognitive outcomes.
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.
authors.affiliation: From the Departments of Pathology (DI, OP, GR, BC, JT), and Neurology (RO, JT), Johns Hopkins University School of Medicine; and Laboratory of Personality and Cognition, Intramural Research Program, National Institute on Aging, National Institutes of Health (SMR, ABZ, YA), Baltimore, Maryland; and Neuropathology Research, Biomedical Research Institute of New Jersey, Cedar Knolls, New Jersey (DI).
authors.forename: Diego
authors.initials: D
authors.lastname: Iacono
authors.forename: Susan M
authors.initials: SM
authors.lastname: Resnick
authors.forename: Richard
authors.initials: R
authors.lastname: O'Brien
authors.forename: Alan B
authors.initials: AB
authors.lastname: Zonderman
authors.forename: Yang
authors.initials: Y
authors.lastname: An
authors.forename: Olga
authors.initials: O
authors.lastname: Pletnikova
authors.forename: Gay
authors.initials: G
authors.lastname: Rudow
authors.forename: Barbara
authors.initials: B
authors.lastname: Crain
authors.forename: Juan C
authors.initials: JC
authors.lastname: Troncoso
mesh_terms: D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001344:Autopsy; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D060825:Cognitive Dysfunction / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D011180:Postmortem Changes; D013238:Stereotaxic Techniques; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016875:tau Proteins