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Relations between brain tissue loss, CSF biomarkers, and the ApoE genetic profile: a longitudinal MRI study.

ABSTRACT: Previously it was reported that Alzheimer's disease (AD) patients have reduced beta amyloid (Abeta(1-42)) and elevated total tau (t-tau) and phosphorylated tau (p-tau(181p)) in the cerebrospinal fluid (CSF), suggesting that these same measures could be used to detect early AD pathology in healthy elderly individuals and those with mild cognitive impairment (MCI). In this study, we tested the hypothesis that there would be an association among rates of regional brain atrophy, the CSF biomarkers Abeta(1-42), t-tau, and p-tau(181p) and apolipoprotein E (ApoE) epsilon4 status, and that the pattern of this association would be diagnosis-specific. Our findings primarily showed that lower CSF Abeta(1-42) and higher tau concentrations were associated with increased rates of regional brain tissue loss and the patterns varied across the clinical groups. Taken together, these findings demonstrate that CSF biomarker concentrations are associated with the characteristic patterns of structural brain changes in healthy elderly and mild cognitive impairment subjects that resemble to a large extent the pathology seen in AD. Therefore, the finding of faster progression of brain atrophy in the presence of lower Abeta(1-42) levels and higher tau levels supports the hypothesis that CSF Abeta(1-42) and tau are measures of early AD pathology. Moreover, the relationship among CSF biomarkers, ApoE epsilon4 status, and brain atrophy rates are regionally varying, supporting the view that the genetic predisposition of the brain to beta amyloid and tau mediated pathology is regional and disease stage specific.

SUBMITTER: Tosun D

PROVIDER: S-EPMC2902689 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Relations between brain tissue loss, CSF biomarkers, and the ApoE genetic profile: a longitudinal MRI study.

Tosun Duygu D Schuff Norbert N Truran-Sacrey Diana D Shaw Leslie M LM Trojanowski John Q JQ Aisen Paul P Peterson Ronald R Weiner Michael W MW

Neurobiology of aging 20100608 8

Previously it was reported that Alzheimer's disease (AD) patients have reduced beta amyloid (Abeta(1-42)) and elevated total tau (t-tau) and phosphorylated tau (p-tau(181p)) in the cerebrospinal fluid (CSF), suggesting that these same measures could be used to detect early AD pathology in healthy elderly individuals and those with mild cognitive impairment (MCI). In this study, we tested the hypothesis that there would be an association among rates of regional brain atrophy, the CSF biomarkers A ...[more]

PMID: 20570401

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Project description:Hippocampal volume change over time, measured with MRI, has huge potential as a marker for Alzheimer's disease. The objectives of this study were: (i) to test if constant and accelerated hippocampal loss can be detected in Alzheimer's disease, mild cognitive impairment and normal ageing over short periods, e.g. 6-12 months, with MRI in the large multicentre setting of the Alzheimer's Disease Neuroimaging Initiative (ADNI); (ii) to determine the extent to which the polymorphism of the apolipoprotein E (ApoE) gene modulates hippocampal change; and (iii) to determine if rates of hippocampal loss correlate with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease, such as the beta-amyloid (Abeta(1-42)) and tau proteins (tau). The MRI multicentre study included 112 cognitive normal elderly individuals, 226 mild cognitive impairment and 96 Alzheimer's disease patients who all had at least three successive MRI scans, involving 47 different imaging centres. The mild cognitive impairment and Alzheimer's disease groups showed hippocampal volume loss over 6 months and accelerated loss over 1 year. Moreover, increased rates of hippocampal loss were associated with presence of the ApoE allele epsilon4 gene in Alzheimer's disease and lower CSF Abeta(1-42) in mild cognitive impairment, irrespective of ApoE genotype, whereas relations with tau were only trends. The power to measure hippocampal change was improved by exploiting correlations statistically between successive MRI observations. The demonstration of considerable hippocampal loss in mild cognitive impairment and Alzheimer's disease patients over only 6 months and accelerated loss over 12 months illustrates the power of MRI to track morphological brain changes over time in a large multisite setting. Furthermore, the relations between faster hippocampal loss in the presence of ApoE allele epsilon4 and decreased CSF Abeta(1-42) supports the concept that increased hippocampal loss is an indicator of Alzheimer's disease pathology and a potential marker for the efficacy of therapeutic interventions in Alzheimer's disease.

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Dataset Information

Relations between brain tissue loss, CSF biomarkers, and the ApoE genetic profile: a longitudinal MRI study.

Publications

Relations between brain tissue loss, CSF biomarkers, and the ApoE genetic profile: a longitudinal MRI study.

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