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

• Published in: Acta neuropathologica 2014-05, Vol.127 (5), p.621-632
• Main Authors: 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.
• Format: Article
• Language: English
• Subjects: Aged; Alzheimer Disease - blood; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - genetics; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Peptides - blood; Amyloid beta-Peptides - cerebrospinal fluid; Apolipoproteins; Apolipoproteins E - blood; Apolipoproteins E - cerebrospinal fluid; Apolipoproteins E - genetics; Atrophy; Biomarkers; Biomarkers - blood; Biomarkers - cerebrospinal fluid; Brain - pathology; Brain research; Cognition; Cognitive Dysfunction - blood; Cognitive Dysfunction - cerebrospinal fluid; Cognitive Dysfunction - genetics; Cognitive Dysfunction - pathology; Dementia; Disease; Disease Progression; Female; Follow-Up Studies; Genotype & phenotype; Gray Matter - pathology; Hemoglobin; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Medical imaging; Medicine; Medicine & Public Health; Neurodegeneration; Neuroimaging; Neurosciences; Original Paper; Pathology; Peptide Fragments - blood; Peptide Fragments - cerebrospinal fluid; Phosphorylation; Plasma; Proteins; Risk factors; Severity of Illness Index; Survival Analysis; tau Proteins - cerebrospinal fluid
• ISSN: 0001-6322; 1432-0533
• DOI: 10.1007/s00401-013-1236-0

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/Aβ 1–42 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.