Abstract
IntroductionLipoprotein-associated phospholipase A2 (Lp-PLA2) is a circulating enzyme with pro-inflammatory and oxidative activities associated with cardiovascular disease and ischemic stroke. While high plasma Lp-PLA2 activity was reported as a risk factor for dementia in the Rotterdam study, no association between Lp-PLA2 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-PLA2 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.MethodsSubjects 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-PLA2 activity between the cognitive diagnosis groups were tested with ANOVA and in multiple linear regression models with adjustment for covariates. Associations between Lp-PLA2 and markers of cardiovascular disease and AD were explored with Spearman's correlation coefficients.ResultsThere was no significant difference in plasma Lp-PLA2 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-PLA2 activity in multiple regression models. Lp-PLA2 activity was correlated with LDL and inversely correlated with high-density lipoprotein (HDL). AD subjects with APOE-ε4 had higher Lp-PLA2 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-PLA2 activity and CSF markers of AD.ConclusionPlasma Lp-PLA2 was not associated with a diagnosis of AD or aMCI in this cross-sectional study. The main clinical correlates of Lp-PLA2 activity in AD, aMCI and cognitively healthy subjects were variables associated with lipid metabolism.
Highlights
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a circulating enzyme with pro-inflammatory and oxidative activities associated with cardiovascular disease and ischemic stroke
The groups differed in terms of age (P = 0.0005), gender (P = 0.02), education (P = 0.0005), homocysteine (P = 0.002), high-density lipoprotein (HDL) (P = 0.005), Scheltens score [16] (P = 0.002), Wahlund score [17] (P = 0.04), Hachinski ischemia score [15] (P < 0.0001), cerebrospinal fluid (CSF) T-tau (P < 0.0001) and CSF P-tau (P < 0.0001); values were higher in the Alzheimer’s disease (AD) group than in the normal control group while values in the amnestic MCI (aMCI) group were intermediate
Differences were detected across the groups for total cholesterol:HDL ratio (P = 0.01) and CSF Ab42 (P < 0.0001); values for these measures were lower in the AD group than in the normal control group and, again, values in the aMCI group were intermediate
Summary
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a circulating enzyme with pro-inflammatory and oxidative activities associated with cardiovascular disease and ischemic stroke. While high plasma Lp-PLA2 activity was reported as a risk factor for dementia in the Rotterdam study, no association between Lp-PLA2 mass and dementia or Alzheimer’s disease (AD) was detected in the Framingham study. Lipoprotein-associated phospholipase A2 (Lp-PLA2), known as platelet activating factor acetylhydrolase (PAFAH), is a circulating enzyme with pro-inflammatory and oxidative activities studied extensively as a marker of cardiovascular risk [1,2,3]. While other cardiovascular risk factors, such as hypertension, hyperlipidemia and diabetes, may increase the risk of developing dementia and Alzheimer’s disease (AD) [4], there is limited published epidemiological data regarding the relationship between Lp-PLA2 activity and dementia. Apolipoprotein E (APOE) polymorphisms related to AD risk influence Lp-PLA2 activity levels [7], yet the null activity polymorphism of the Lp-PLA2 gene was not associated with lower risk of AD in a large casecontrol study in Japan [8]
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