title: Plasma lipoprotein-associated phospholipase A2 activity in Alzheimer's disease, amnestic mild cognitive impairment, and cognitively healthy elderly subjects: a cross-sectional study.
abstract: BACKGROUND
  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. 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.
  
  
  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-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.
  
  
  RESULTS
  There 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.
  
  
  CONCLUSIONS
  Plasma 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.
authors.affiliation: Worldwide Epidemiology, GlaxoSmithKline R&D, 1-3 Iron Bridge Road, Stockley Park, UB11 1BT, UK ; Memory Clinic, Department of Geriatrics, Basel University Hospital, Schanzenstrasse 55, 4031 Basel, Switzerland.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Davidson
authors.affiliation: R&D China, GlaxoSmithKline, Addenbrooke's Centre for Clinical Investigation, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2GG, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Lockhart
authors.affiliation: Genetics, GlaxoSmithKline R&D, 5 Moore Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Amos
authors.affiliation: Worldwide Epidemiology, GlaxoSmithKline R&D, 1-3 Iron Bridge Road, Stockley Park, UB11 1BT, UK.
authors.forename: Heide A
authors.initials: HA
authors.lastname: Stirnadel-Farrant
authors.affiliation: Genetics, GlaxoSmithKline R&D, 709 Swedeland Road, King of Prussia, PA 19406, USA.
authors.forename: Vincent
authors.initials: V
authors.lastname: Mooser
authors.affiliation: Memory Clinic, Department of Geriatrics, Basel University Hospital, Schanzenstrasse 55, 4031 Basel, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Sollberger
authors.affiliation: Laboratory Medicine, Basel University Hospital, Basel, Switzerland.
authors.forename: Axel
authors.initials: A
authors.lastname: Regeniter
authors.affiliation: Memory Clinic, Department of Geriatrics, Basel University Hospital, Schanzenstrasse 55, 4031 Basel, Switzerland.
authors.forename: Andreas U
authors.initials: AU
authors.lastname: Monsch
authors.affiliation: Worldwide Epidemiology, GlaxoSmithKline R&D, 5 Moore Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Irizarry