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).
Conclusion: 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.
