Reduced levels of cholesterol, phospholipids, and fatty acids in cerebrospinal fluid of Alzheimer disease patients are not related to apolipoprotein E4

Apolipoprotein E4 (apoE4) has been identified as a major risk factor for Al zheimer disease (AD). Previously it has been reported that levels of apoE a re reduced in cerebrospinal fluid (CSF) of AD patients. Because it is known that apoE4 affects plasma lipid metabolism, we examined whether the presen ce of apoE4 might correlate with an altered lipid metabolism in the CSF of control subjects and AD patients. ApoE and lipid concentrations were determ ined in postmortem ventricular CSF of 30 neuropathologically confirmed AD c ases and 31 age-matched control patients. ApoE genotyping was performed on frozen brain tissue of the same patients. In line with other reports, we fo und an increased APOE*4 allele frequency in the AD group (0.461) when compa red with the control group (0.225). ApoE levels in CSF of AD patients were not significantly reduced when compared with the controls (mean +/- SD: 63 +/- 55 and 82 +/- 62 mu g/dL for AD and controls, respectively). However, i n the CSF of AD patients levels of free and esterified cholesterol (0.13 +/ - 0.09 and 0.25 +/- 0.19 mg/dL, and 0.25 +/- 0.19 and 0.42 +/- 0.34, respec tively), phospholipids (0.2 +/- 0.1 and 3.5 +/- 5.0 mg/dL) and, surprisingl y, also fatty acids (4.5 +/- 3.2 and 28.0 +/- 18.5 mu mol/L) were found to be significantly reduced. After correction for age, sex, postmortem delay, and pH the levels of phospholipids, fatty acids, and free cholesterol were still significantly reduced (p = 0.021,p = 0.026, and p = 0.012, respective ly). The apoE and lipid levels in CSF of AD-and control patients appeared n ot to be affected by the number of APOE*4 alleles. In conclusion, our resul ts suggest an altered lipid homeostasis in the brain of AD patients that is not related to the presence of apoE4. It is, therefore, unlikely that an e ffect of apoE4 on brain lipid metabolism is the underlying mechanism behind the role of apoE4 in the development of AD.