Contribution of changes in ubiquitin and myelin basic protein to age-related cognitive decline

Document Type

Article

Abstract

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.

Medical Subject Headings

Aged; Aged, 80 and over; Aging (metabolism); Alzheimer Disease (metabolism); Blotting, Western; Chi-Square Distribution; Cognition Disorders (metabolism); Female; Frontal Lobe (anatomy & histology, metabolism); Humans; Immunoblotting; Immunohistochemistry; Male; Myelin Basic Protein (metabolism); Neurologic Examination; Neuropsychological Tests; Statistics, Nonparametric; Ubiquitin (metabolism)

Publication Date

1-1-2004

Publication Title

Neuroscience research

ISSN

0168-0102

Volume

48

Issue

1

First Page

93

Last Page

100

PubMed ID

14687885

Digital Object Identifier (DOI)

10.1016/j.neures.2003.10.002

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