Contribution of changes in ubiquitin and myelin basic protein to age-related cognitive decline.
The structural substrates for age-associated cognitive and motor slowing are not known, but age-related white matter changes, such as ubiquitin (UBQ)-immunoreactive granular degeneration of myelin, might contribute to this slowing. To address this hypothesis we measured immunoreactivity for UBQ and myelin basic protein (MBP) in frontal white matter of age-, sex- and postmortem interval-matched cases with no cognitive impairment (NCI; N=12), mild cognitive impairment (MCI; N=14) and Alzheimer disease (AD; N=12). There were no significant correlations between UBQ in white matter and cognitive measures, but MBP was significantly lower in AD compared with NCI and MCI. MBP correlated with overall cognition as assessed by neuropsychological summary scores, as well as with timed cognitive tests and those that reflect frontal functions. An age-related decrease in MBP immunoreactivity was detected in NCI cases (r=0.71). These results support the hypothesis that white matter pathology may contribute to age-associated decline in cognition.
Wang
Deng-Shun
DS
Department of Neuroscience and Pathology (Neuropathology), Birdsall 317, Mayo Clinic Jacksonville, 4500 Sam Pablo Road, Jacksonville, FL 32224, USA.
Bennett
David A
DA
Mufson
Elliott J
EJ
Mattila
Petri
P
Cochran
Elizabeth
E
Dickson
Dennis W
DW
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism; D015153:Blotting, Western; D016009:Chi-Square Distribution; D003072:Cognition Disorders / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000033:anatomy & histology / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D004676:Myelin Basic Protein / Q000378:metabolism*; D009460:Neurologic Examination; D009483:Neuropsychological Tests; D018709:Statistics, Nonparametric; D025801:Ubiquitin / Q000378:metabolism*
D004676:Myelin Basic Protein; D025801:Ubiquitin