Endocannabinoids in Alzheimer's disease and their impact on normative cognitive performance: a case-control and cohort study.
BACKGROUND
Neuropathological, animal, and cell culture studies point to a role for the body's own endogenous cannabinoids (eCBs) system in Alzheimer's disease (AD) pathology and treatment. To date, no published studies have investigated the potential utility of circulating eCBs as diagnostic biomarkers for AD or the impact of central eCBs on cognition.


RESULTS
In comparison with healthy controls, there were no significant differences in measured eCB concentrations in plasma samples from patients with AD. Detectable eCBs in cerebrospinal fluid (CSF) had no relationship to cognitive performance in healthy controls at risk for AD. In pooled plasma samples, an inverse correlation was observed between plasma levels of the eCB 2-AG (2-arachidonoylglycerol) and TNF-alpha (r = -0.41, p < 0.02).


CONCLUSIONS
These results suggest that circulating endocannabinoids do not have utility as diagnostic biomarkers for AD and do not have a robust correlation with cognitive performance. Circulating levels of 2-AG may downregulate TNF-alpha production.
Koppel
Jeremy
J
The Litwin-Zucker Research Center for the Study of Alzheimer's Disease and Memory Disorders, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA. jkoppel@lij.edu
Bradshaw
Heather
H
Goldberg
Terry E
TE
Khalili
Houman
H
Marambaud
Philippe
P
Walker
Michael J
MJ
Pazos
Miguel
M
Gordon
Marc L
ML
Christen
Erica
E
Davies
Peter
P
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000175:diagnosis*; D001095:Arachidonic Acids; D015415:Biomarkers / Q000097:blood; D063385:Cannabinoid Receptor Modulators / Q000097:blood*; D016022:Case-Control Studies; D003072:Cognition Disorders; D015331:Cohort Studies; D015536:Down-Regulation; D063388:Endocannabinoids; D005260:Female; D005989:Glycerides; D006801:Humans; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D001095:Arachidonic Acids; D015415:Biomarkers; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D014409:Tumor Necrosis Factor-alpha; C094503:glyceryl 2-arachidonate