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Alzheimer's

Lipids Health Dis. 2009 Jan 14;8:2.

Endocannabinoids in Alzheimer's Disease and Their Impact on Normative Cognitive Performance: A Case-Control and Cohort Study.

Koppel J, Bradshaw H, Goldberg TE, Khalili H, Marambaud P, Walker MJ, Pazos M, Gordon ML, Christen E, Davies P.

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.

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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).

CONCLUSION: 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.

PMCID: PMC2631501, PMID: 19144193 [PubMed - indexed for MEDLINE]

http://www.lipidworld.com/content/8/1/2

 


 

British Journal of Pharmacology (2007) 152, 655–662

Alzheimer’s disease; taking the edge off with cannabinoids?

VA Campbell and A Gowran

Department of Physiology and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland

Alzheimer’s disease is an age-related neurodegenerative condition associated with cognitive decline. The pathological hallmarks of the disease are the deposition of β-amyloid protein and hyperphosphorylation of tau, which evoke neuronal cell death and impair inter-neuronal communication. The disease is also associated with neuroinflammation, excitotoxicity and oxidative stress. In recent years the proclivity of cannabinoids to exert a neuroprotective influence has received substantial interest as a means to mitigate the symptoms of neurodegenerative conditions. In brains obtained from Alzheimer’s patients alterations in components of the cannabinoid system have been reported, suggesting that the cannabinoid system either contributes to, or is altered by, the pathophysiology of the disease. Certain cannabinoids can protect neurons from the deleterious effects of β-amyloid and are capable of reducing tau phosphorylation. The propensity of cannabinoids to reduce β-amyloid-evoked oxidative stress and neurodegeneration, whilst stimulating neurotrophin expression neurogenesis, are interesting properties that may be beneficial in the treatment of Alzheimer’s disease. Δ9-tetrahydrocannabinol can also inhibit acetylcholinesterase activity and limit amyloidogenesis which may improve cholinergic transmission and delay disease progression. Targeting cannabinoid receptors on microglia may reduce the neuroinflammation that is a feature of Alzheimer’s disease, without causing psychoactive effects. Thus, cannabinoids offer a multi-faceted approach for the treatment of Alzheimer’s disease by providing neuroprotection and reducing neuroinflammation, whilst simultaneously supporting the brain’s intrinsic repair mechanisms by augmenting neurotrophin expression and enhancing neurogenesis. The evidence supporting a potential role for the cannabinoid system as a therapeutic target for the treatment of Alzheimer’s disease will be reviewed herewith.

PMCID: PMC2190031, PMID: 17828287 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2190031/

 


 

Mol Pharm. 2006 Nov-Dec;3(6):773-7.

A Molecular Link Between the Active Component of Marijuana and Alzheimer's Disease Pathology.

Eubanks LM, Rogers CJ, AE Beuscher IV, Koob GF, Olson AJ, Dickerson TJ, Janda KD.

Department of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA.

Alzheimer's disease is the leading cause of dementia among the elderly, and with the ever-increasing size of this population, cases of Alzheimer's disease are expected to triple over the next 50 years. Consequently, the development of treatments that slow or halt the disease progression have become imperative to both improve the quality of life for patients and reduce the health care costs attributable to Alzheimer's disease. Here, we demonstrate that the active component of marijuana, Delta9-tetrahydrocannabinol (THC), competitively inhibits the enzyme acetylcholinesterase (AChE) as well as prevents AChE-induced amyloid beta-peptide (Abeta) aggregation, the key pathological marker of Alzheimer's disease. Computational modeling of the THC-AChE interaction revealed that THC binds in the peripheral anionic site of AChE, the critical region involved in amyloidgenesis. Compared to currently approved drugs prescribed for the treatment of Alzheimer's disease, THC is a considerably superior inhibitor of Abeta aggregation, and this study provides a previously unrecognized molecular mechanism through which cannabinoid molecules may directly impact the progression of this debilitating disease.

http://www.ncbi.nlm.nih.gov/pubmed/17140265