title: Elevation of Plasma 2-Arachidonoylglycerol Levels in Alzheimer's Disease Patients as a Potential Protective Mechanism against Neurodegenerative Decline.
abstract: BACKGROUND
  Growing evidence suggests that the endocannabinoid system is involved in the pathogenesis of Alzheimer's disease (AD) and atherosclerosis.
  
  
  OBJECTIVE
  The purpose of this study was to investigate the activation of the endocannabinoid system in AD in vivo and the possible intermediate role of atherosclerosis.
  
  
  METHODS
  We enrolled 41 patients with probable AD, and 30 age- and gender-matched controls. All subjects underwent: ultrasound examination of cerebral and neck vessels (including intima-media thickness and plaque stenosis evaluation); blood sampling to measure levels of endocannabinoid [anandamide (AEA), 2-arachidonoylglycerol (2-AG)] and endogenous AEA analogues [N-palmitoyl-ethanolamide (PEA); N-oleoyl-ethanolamide]; neuropsychological evaluation and brain MRI (atrophy, white matter hyperintensity volume).
  
  
  RESULTS
  2-AG levels were higher in AD patients compared to controls (Mann-Whitney test p = 0.021). In the AD group, 2-AG correlated to white matter hyperintensity volume (r = 0.415, p = 0.015) and was higher in patients with chronic heart ischemic disease (p = 0.023). In AD patients, 2-AG was also positively related to memory (r = 0.334, p = 0.05) and attention (r = 0.423, p = 0.018) performances. Constructional praxia test scores were lower in patients with higher levels of PEA (r =-0.389, p = 0.019).
  
  
  CONCLUSIONS
  AD patients present high plasma 2-AG levels, also in relation to heart ischemic disease and cerebral leukoaraiosis. This may be a protective mechanism hindering neurodegeneration, but it may also play an ambivalent role on cerebrovascular circulation. The increase in 2-AG and PEA levels observed with ongoing pathological processes may differently modulate cognitive performances.
authors.forename: Claudia
authors.initials: C
authors.lastname: Altamura
authors.forename: Mariacarla
authors.initials: M
authors.lastname: Ventriglia
authors.forename: Maria Giulia
authors.initials: MG
authors.lastname: Martini
authors.forename: Domenico
authors.initials: D
authors.lastname: Montesano
authors.forename: Yuri
authors.initials: Y
authors.lastname: Errante
authors.forename: Fabiana
authors.initials: F
authors.lastname: Piscitelli
authors.forename: Federica
authors.initials: F
authors.lastname: Scrascia
authors.forename: Carlo
authors.initials: C
authors.lastname: Quattrocchi
authors.forename: Paola
authors.initials: P
authors.lastname: Palazzo
authors.forename: Serenella
authors.initials: S
authors.lastname: Seccia
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Vernieri
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000000981:diagnostic imaging; D001095:Arachidonic Acids / Q000097:blood*; D001288:Attention; D015415:Biomarkers; D001921:Brain / Q000098:blood supply*; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D002560:Cerebrovascular Circulation; D003430:Cross-Sectional Studies; D063388:Endocannabinoids / Q000097:blood*; D005260:Female; D005989:Glycerides / Q000097:blood*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory; D009483:Neuropsychological Tests
chemical_list: D001095:Arachidonic Acids; D015415:Biomarkers; D063388:Endocannabinoids; D005989:Glycerides; C094503:glyceryl 2-arachidonate
keywords: Alzheimer’s disease; atherosclerosis; endocannabinoids; leukoaraiosis