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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 -ε4 had higher Lp-PLA 2  activity (207.9 (SD 41.2)) than AD subjects lacking  APOE -ε4 (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.

alzheimer's research and therapy

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