CSF Apo-E levels associate with cognitive decline and MRI changes
Autor: | Toledo, Jon B, Da, Xiao, Weiner, Michael W, Wolk, David A, Xie, Sharon X, Arnold, Steven E, Davatzikos, Christos, Shaw, Leslie M, Trojanowski, John Q, Alzheimer’s Disease Neuroimaging Initiative |
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Rok vydání: | 2014 |
Předmět: |
Male
Aging Clinical Sciences tau Proteins Neurodegenerative Alzheimer's Disease Severity of Illness Index Plasma Apolipoproteins E Cognition Alzheimer Disease Clinical Research Acquired Cognitive Impairment Genetics Humans 2.1 Biological and endogenous factors Cognitive Dysfunction Longitudinal Studies Phosphorylation Gray Matter Aetiology Neurodegeneration Aged Amyloid beta-Peptides Neurology & Neurosurgery Neurosciences Brain Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) Beta amyloid Alzheimer’s Disease Neuroimaging Initiative Magnetic Resonance Imaging Survival Analysis Peptide Fragments Brain Disorders Cerebrospinal fluid Neurological Disease Progression Female Dementia Atrophy Tau Biomarkers APOE Follow-Up Studies MRI |
Zdroj: | Acta neuropathologica, vol 127, iss 5 |
Popis: | 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 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/Aβ1-42 ratio and APOE genotype-adjusted analyses. In analyses stratified by APOE genotype, our results were only significant in the group without the ε4 allele. Baseline CSF Apo-E levels did not predict longitudinal CSF Aβ 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. |
Databáze: | OpenAIRE |
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