P3‐173: Apolipoproteins and Apolipoprotein Subtypes in Human Cerebrospinal Fluid and Plasma
Year: 2016
Type: article
Study design: Observational Study
Abstract: Apolipoproteins (apo), including apoE and apoJ are linked with Alzheimer’s disease (AD)-risk in genetic studies. Apolipoproteins, including also plasma-derived apoA-I and apoC-III, circulate in both cerebrospinal fluid (CSF) and plasma, but plasma levels may not reflect CSF levels very well. We speculate that subtypes of apolipoproteins have differential metabolic functions based on their associated protein cargo. For example, mixed findings regarding the association of total plasma apoE and AD could be because, in plasma, apoE can complex with both apoB (LDL) and apoAI (HDL), two lipoproteins with opposing associations with AD. We aimed to investigate correlations of apolipoprotein subtype concentrations in plasma and CSF. Dementia-free participants were recruited between 2009 and 2015 from patients presenting to the emergency department with acute headache at the University Hospital Kiel, Germany. Absence of meningoencephalitis was confirmed by lumbar puncture. Age- and sex-adjusted correlations of total apoA-I, J, E and C-III and their subtypes were determined in paired plasma and CSF samples from 12 men and 13 women (mean age=37; 20-76 years). Concentrations of apolipoproteins in CSF were between 0.01% (apoC-III) and 11% (apoE without apoC-III) of the concentration in plasma. CSF and plasma levels of total apolipoproteins and subtypes correlated moderately (≥0.4) except for apoE (Table 1). The plasma subtype of apoA-I with apoC-III most strongly correlated with total CSF apoC-III (r=0.57, p=0.01; Table 2), compared to total plasma apoC-III (r=0.47, p=0.03) or plasma apoE with apoC-III (r=0.44, p=0.04). Total CSF apoE did not correlate with plasma total apolipoproteins or any of the subtypes (Table 3), whereas total CSF apoJ correlated strongest with apoA-I without apoJ in plasma (Table 4). Concordant with previous observations, the minimal correlation of plasma and CSF apoE supports its intrathecal synthesis. Plasma apoA-I containing apoC-III, but not total plasma apoC-III correlated with CSF apoC-III, suggesting increased active transport of apoC-III over the blood-brain barrier in presence of cofactors like apoA-I. CSF levels of some apolipoproteins might be better reflected by specific apolipoprotein subtypes than total plasma concentrations, supporting the necessity of further investigation of apolipoprotein subtypes in in relation to AD risk.
Source: Alzheimer s & Dementia
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2535758405