Measurement of apolipoprotein E (apoE) in cerebrospinal fluid

Apolipoprotein E (apoE) is a protein involved in transport of lipids and ha s been implicated to play an important role in regeneration after nerve inj ury. Determination of apoE in cerebrospinal fluid (CSF) thus have a potenti al interest when studying different forms of brain damage and as a marker o f ongoing regenerative processes in the brain. However, previous studies on CSF ApoE in Alzheimer's disease (AD) have given inconclusive results. Such inconsistant results might be related to confounding factors interfering w ith sample handling and/or analyses, which have not been fully elucidated. We therefore examined different potential confounding factors for analyses of apoE in CSF and also developed a new enzyme linked immunosorbent assay ( ELISA). The hydrophobic character of ApoE resulted in adsorbtion to differe nt types of test tubes commonly used for collection of CSF at lumbar punctu re, resulting in falsly low levels. This makes CSF handling critical, espec ially if samples are taken in different types of tubes, or is transferred t o new tubes. Taking this confounding factors in consideration and analysing patient and control CSF handled in the same way and using the new ELISA, w e could confirm our previous finding of reduced levels of ApoE in AD, (3.4 +/- 1.3mg/l) compared with controls (4.5 +/- 2.7mg/l) (p = 0.045), Both in the AD and in the control group, higher levels of CSF-ApoE was found in ind ividuals possessing the ApoE4 alleles. Our results support that CSF-ApoE is reduced in AD, and that handling of CSF is a critical factor, which may ex plain the discrepant results from previous studies. Differences in the amou nt of patients and controls possessing the ApoE4 allele included might also increase the variance between different studies.