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Published on: November 14, 2017
Relations between brain tissue loss, CSF biomarkers, and the ApoE genetic profile: a longitudinal MRI study
Duygu Tosun1, Norbert Schuff, Diana Truran-Sacrey
1Center for Imaging of Neurodegenerative Diseases, Department of Veterans Affairs Medical Center, San Francisco, CA 94121, United States. duygu.tosun@ucsf.edu
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.
Insights
Cerebrospinal fluid (CSF) biomarkers, including beta-amyloid and tau, correlate with brain atrophy rates in individuals with mild cognitive impairment and healthy elderly. These findings support their use in detecting early Alzheimer's disease (AD) pathology.
Area of Science:
- Neuroscience
- Biomarkers
- Neurodegenerative Diseases
Background:
- Alzheimer's disease (AD) is characterized by specific cerebrospinal fluid (CSF) biomarker profiles: reduced beta-amyloid (Abeta(1-42)) and elevated total tau (t-tau) and phosphorylated tau (p-tau(181p)).
- These CSF markers are potential indicators for early AD pathology in healthy elderly and mild cognitive impairment (MCI) populations.
Purpose of the Study:
- To investigate the association between CSF biomarkers (Abeta(1-42), t-tau, p-tau(181p)), regional brain atrophy rates, and apolipoprotein E (ApoE) epsilon4 status.
- To determine if these associations are diagnosis-specific across clinical groups.
Main Methods:
- Analysis of CSF biomarker concentrations (Abeta(1-42), t-tau, p-tau(181p)) in relation to regional brain atrophy rates.
- Assessment of apolipoprotein E (ApoE) epsilon4 status.
- Comparison of biomarker-atrophy patterns across healthy elderly, MCI, and AD groups.
Main Results:
- Lower CSF Abeta(1-42) and higher tau levels were significantly associated with increased rates of regional brain tissue loss.
- The patterns of association between CSF biomarkers and brain atrophy varied across clinical diagnoses (healthy elderly, MCI, AD).
- Regional variations were observed in the relationships among CSF biomarkers, ApoE epsilon4 status, and brain atrophy rates.
Conclusions:
- CSF biomarker concentrations are linked to characteristic structural brain changes in healthy elderly and MCI subjects, mirroring AD pathology.
- Elevated tau and reduced Abeta(1-42) in CSF are indicative of early AD pathology and predict faster brain atrophy progression.
- The interplay between CSF biomarkers, genetic predisposition (ApoE epsilon4), and brain atrophy is regional and disease-stage specific.
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