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CSF Apo-E levels associate with cognitive decline and MRI changes.

ABSTRACT: Apolipoprotein E (APOE) ?4 allele is the most important genetic risk factor for Alzheimer's disease (AD) and it is thought to do so by modulating levels of its product, apolipoprotein E (Apo-E), and regulating amyloid-? (A?) clearance. However, information on clinical and biomarker correlates of Apo-E proteins is scarce. We examined the relationship of cerebrospinal fluid (CSF) and plasma Apo-E protein levels, and APOE genotype to cognition and AD biomarker changes in 311 AD neuroimaging initiative subjects with CSF Apo-E measurements and 565 subjects with plasma Apo-E measurements. At baseline, higher CSF Apo-E levels were associated with higher total and phosphorylated CSF tau levels. CSF Apo-E levels were associated with longitudinal cognitive decline, MCI conversion to dementia, and gray matter atrophy rate in total tau/A?1-42 ratio and APOE genotype-adjusted analyses. In analyses stratified by APOE genotype, our results were only significant in the group without the ?4 allele. Baseline CSF Apo-E levels did not predict longitudinal CSF A? or tau changes. Plasma Apo-E levels show a mild correlation with CSF Apo-E levels, but were not associated with longitudinal cognitive and MRI changes. Based on our analyses, we speculate that increased CSF Apo-E2 or -E3 levels might represent a protective response to injury in AD and may have neuroprotective effects by decreasing neuronal damage independent of tau and amyloid deposition in addition to its effects on amyloid clearance.

SUBMITTER: Toledo JB

PROVIDER: S-EPMC3988233 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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CSF Apo-E levels associate with cognitive decline and MRI changes.

Toledo Jon B JB Da Xiao X Weiner Michael W MW Wolk David A DA Xie Sharon X SX Arnold Steven E SE Davatzikos Christos C Shaw Leslie M LM Trojanowski John Q JQ

Acta neuropathologica 20140103 5

Apolipoprotein E (APOE) ε4 allele is the most important genetic risk factor for Alzheimer's disease (AD) and it is thought to do so by modulating levels of its product, apolipoprotein E (Apo-E), and regulating amyloid-β (Aβ) clearance. However, information on clinical and biomarker correlates of Apo-E proteins is scarce. We examined the relationship of cerebrospinal fluid (CSF) and plasma Apo-E protein levels, and APOE genotype to cognition and AD biomarker changes in 311 AD neuroimaging initiat ...[more]

PMID: 24385135

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CSF Apo-E levels associate with cognitive decline and MRI changes.

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CSF Apo-E levels associate with cognitive decline and MRI changes.

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