Plasma lipoprotein-associated phospholipase A2 activity in Alzheimer's disease, amnestic mild cognitive impairment, and cognitively healthy elderly subjects: a cross-sectional study

Introduction: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a circulating enzyme with pro-inflammatory and oxidative activities associated with cardiovascular disease and ischemic stroke. While high plasma Lp-PLA(2) activity was reported as a risk factor for dementia in the Rotterdam study, no association between Lp-PLA(2) mass and dementia or Alzheimer's disease (AD) was detected in the Framingham study. The objectives of the current study were to explore the relationship of plasma Lp-PLA(2) activity with cognitive diagnoses (AD, amnestic mild cognitive impairment (aMCI), and cognitively healthy subjects), cardiovascular markers, cerebrospinal fluid (CSF) markers of AD, and apolipoprotein E (APOE) genotype. Methods: Subjects with mild AD (n = 78) and aMCI (n = 59) were recruited from the Memory Clinic, University Hospital, Basel, Switzerland; cognitively healthy subjects (n = 66) were recruited from the community. Subjects underwent standardised medical, neurological, neuropsychological, imaging, genetic, blood and CSF evaluation. Differences in Lp-PLA(2) activity between the cognitive diagnosis groups were tested with ANOVA and in multiple linear regression models with adjustment for covariates. Associations between Lp-PLA(2) and markers of cardiovascular disease and AD were explored with Spearman's correlation coefficients. Results: There was no significant difference in plasma Lp-PLA(2) activity between AD (197.1 (standard deviation, SD 38.4) nmol/min/ml) and controls (195.4 (SD 41.9)). Gender, statin use and low-density lipoprotein cholesterol (LDL) were independently associated with Lp-PLA(2) activity in multiple regression models. Lp-PLA(2) activity was correlated with LDL and inversely correlated with high-density lipoprotein (HDL). AD subjects with APOE-e4 had higher Lp-PLA(2) activity (207.9 (SD 41.2)) than AD subjects lacking APOE-e4 (181.6 (SD 26.0), P = 0.003) although this was attenuated by adjustment for LDL (P = 0.09). No strong correlations were detected for Lp-PLA(2) activity and CSF markers of AD. Conclusion: Plasma Lp-PLA(2) was not associated with a diagnosis of AD or aMCI in this cross-sectional study. The main clinical correlates of Lp-PLA(2) activity in AD, aMCI and cognitively healthy subjects were variables associated with lipid metabolism.