title: CSF Apo-E levels associate with cognitive decline and MRI changes.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, HUP, Maloney 3rd, 36th and Spruce Streets, Philadelphia, PA, 19104-4283, USA.
authors.forename: Jon B
authors.initials: JB
authors.lastname: Toledo
authors.forename: Xiao
authors.initials: X
authors.lastname: Da
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.forename: David A
authors.initials: DA
authors.lastname: Wolk
authors.forename: Sharon X
authors.initials: SX
authors.lastname: Xie
authors.forename: Steven E
authors.initials: SE
authors.lastname: Arnold
authors.forename: Christos
authors.initials: C
authors.lastname: Davatzikos
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid* / Q000235:genetics / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000097:blood / Q000134:cerebrospinal fluid; D001057:Apolipoproteins E / Q000097:blood / Q000134:cerebrospinal fluid* / Q000235:genetics; D001284:Atrophy; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001921:Brain / Q000473:pathology*; D003071:Cognition; D060825:Cognitive Dysfunction / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D010446:Peptide Fragments / Q000097:blood / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D012720:Severity of Illness Index; D016019:Survival Analysis; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins