Scientists Discover How Cannabis Slows Alzheimer’s Disease

[dddaver]

This is one of the main reasons I grow and smoke/vape. Years ago I read cannabis may have a prophylactic action on those nerves most susceptible to the disease. I had old relatives get this. Terrible. I do crosswords too. Scary. Maybe I should ingest oil once in a while as a preventative. Scares the shit out of me and I will do anything to prevent it. This is another one of those many, many things we should is NOT accept as a "normal part of aging."

 

[nattynattygurrl]

Glad to have one more reason to be grateful that my Dad tokes!!

…

I love that we all have this place to gather, share and support each other through scary stuff like this!

 

[trichrider]

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


Lisa M. Eubanks,† Claude J. Rogers,† Albert E. Beuscher, IV,‡ George F. Koob,§ Arthur J. Olson,‡ Tobin J. Dickerson,† and Kim D. Janda†

The publisher's final edited version of this article is available at Mol Pharm

Abstract.

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 as well as reduce the health care costs attributable to Alzheimer's disease. Here, we demonstrate that the active component of marijuana, Δ9-tetrahydrocannabinol (THC), competitively inhibits the enzyme acetylcholinesterase (AChE) as well as prevents AChE-induced amyloid β-peptide (Aβ) 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 Aβ aggregation, and this study provides a previously unrecognized molecular mechanism through which cannabinoid molecules may directly impact the progression of this debilitating disease.

Introduction.

Since the characterization of the Cannabis sativa-produced cannabinoid, Δ9-tetrahydrocannabinol (THC) (Figure 1), in the 1960's,1 this natural product has been widely explored as an anti-emetic, anti-convulsive, anti-inflammatory, and analgesic.2 In these contexts, efficacy results from THC binding to the family of cannabinoid receptors found primarily on central and peripheral neurons (CB1) or immune cells (CB2).3 More recently, a link between the endocannabinoid system and Alzheimer's disease has been discovered4 which has provided a new therapeutic target for the treatment of patients suffering from Alzheimer's disease.5 New targets for this debilitating disease are critical as Alzheimer's disease afflicts over 20 million people worldwide, with the number of diagnosed cases continuing to rise at an exponential rate.6,7 These studies have demonstrated the ability of cannabinoids to provide neuroprotection against β-amyloid peptide (Aβ) toxicity.8-10 Yet, it is important to note that in these reports, cannabinoids serve as signaling molecules which regulate downstream events implicated in Alzheimer's disease pathology and are not directly implicated as effecting Aβ at a molecular level.

Chemical structure of Δ9-tetrahydrocannabinol (THC).

One of the primary neuropathological hallmarks of Alzheimer's disease is deposition of Aβ into amyloid plaques in areas of the brain important for memory and cognition.11 Over the last two decades, the etiology of Alzheimer's disease has been elucidated through extensive biochemical and neurobiological studies, leading to an assortment of possible therapeutic strategies including prevention of downstream neurotoxic events, interference with Aβ metabolism, and reduction of damage from oxidative stress and inflammation.12 The impairment of the cholinergic system is the most dramatic of the neurotransmitter systems affected by Alzheimer's disease and as a result, has been thoroughly investigated. Currently, there are four FDA-approved drugs that treat the symptoms of Alzheimer's disease by inhibiting the active site of acetylcholinesterase (AChE), the enzyme responsible for the degradation of acetylcholine, thereby raising the levels of neurotransmitter in the synaptic cleft.13 In addition, AChE has been shown to play a further role in Alzheimer's disease by acting as a molecular chaperone, accelerating the formation of amyloid fibrils in the brain and forming stable complexes with Aβ at a region known as the peripheral anionic binding site (PAS).14,15 Evidence supporting this theory was provided by studies demonstrating that the PAS ligand, propidium, is able to prevent amyloid acceleration in vitro, whereas active-site inhibitors had no effect.16 Due to the association between the AChE PAS and Alzheimer's disease, a number of studies have focused on blocking this allosteric site.17 Recently, we reported a combined computational and experimental approach to identify compounds containing rigid, aromatic scaffolds hypothesized to disrupt protein-protein interactions.18-20 Similarly, THC is highly lipophilic in nature and possesses a fused tricyclic structure. Thus, we hypothesized that this terpenoid also could bind to the allosteric PAS of AChE with concomitant prevention of AChE-promoted Aβ aggregation.

Experimental Section.


Docking procedures

THC was docked to the mouse AChE structure (PDB ID code 1J07) using AutoDock 3.0.5.21 Twenty docking runs (100 million energy evaluations each) were run with a 26.25 Å × 18.75 Å × 26.25 Å grid box with 0.375 Å grid spacing. This grid box was designed to include regions of both the catalytic site and the peripheral anionic site. Otherwise, standard docking settings were used for the AutoDock calculations, as previously detailed.18


Acetylcholinesterase inhibition studies

All assays were performed using a Cary 50 Bio UV-visible spectrophotometer using an 18-cell changer, and conducted at 37 °C, using a Cary PCB 150 Water Peltier System. Solutions of acetylthiocholine iodide (ATCh iodide) and 5,5′-dithio-bis-(2-nitrobenzoic) acid (DTNB) were prepared according to the method of Ellman, et al.22 Stock solutions of acetylcholinesterase from E. electricus were prepared by dissolving commercially available enzyme in 1% gelatin. Prior to use, an aliquot of the gelatin solution was diluted 1:200 in water. For the assay, the solution was diluted until enzyme activity between 0.10-0.13 AU/min at 500 μM ACTh iodide was obtained. Compounds were prepared as solutions in methanol.

Assays were performed by mixing AChE, THC, and 340 μM DTNB in 100 mM phosphate buffer, pH 8.0, containing 5% methanol. Solutions were incubated at 37 °C for five minutes before the reaction was initiated by the addition of ATCh iodide (75 – 300 μM). The increase of absorbance at 412 nm was monitored for 2 to 5 min. All assays were run in triplicate. Initial rates were determined by subtracting the average observed initial rate from the non-enzymatic reaction.

Linear regression analysis of reciprocal plots of 1/νo versus 1/ for four THC concentrations was performed using Microsoft Excel software. The slope1/v was plotted against to give Ki values. Propagation of error was performed to determine the error, ΔKi.

For studies to determine the mutual exclusivity of THC and propidium iodide, experiments were performed identically to simple THC inhibition studies with a fixed concentration of ACTh iodide (125 μM), and varied concentrations of propidium iodide (0-25 μM) and THC (0-15 μM).


AChE-induced β-amyloid peptide aggregation in the presence of AChE ligands

The aggregation of the β-amyloid peptide was measured using the thioflavin T-based fluorometric assay as described by LeVine23 and Bartolini.16 Assays were measured using a SpectraMAX Gemini fluorescence plate reader with SOFTmax PRO 2.6.1 software. Aβ1-40 stock solutions were prepared in DMSO and HuAChE stocks prepared in distilled water. All stock solutions of Aβ and HuAChE were used immediately after preparation.

In a 96-well plate, triplicate samples of a 20 μL solution of 23 nM of Aβ, 2.30 μM HuAChE and various concentrations of THC in 0.215 M sodium phosphate buffer, pH 8.0 were prepared. These solutions were incubated at room temperature along with triplicate solutions of Aβ alone, Aβ and AChE, and Aβ plus THC at various concentrations. After 48 h, a 2 μL aliquot was removed from each well, placed in a black-walled, clear-bottomed 96-well plate, and diluted with 50 mM glycine-NaOH buffer, pH 8.5, containing 1.5 μM thioflavin T to a total volume of 200 μL. After incubating for 5 min, the fluorescence was measured using λexc = 466 nm and λem = 490 nm with excitation and emission slits of 2 nm. The fluorescence emission spectrum was recorded between 450 and 600 nm, with excitation at 446 nm.

The fluorescence intensities were averaged, and the average background fluorescence of buffer only, or buffer and THC, was subtracted. The corrected fluorescence values were plotted with their standard deviation. The equation, Fi/Fo × 100%, where Fi is the fluorescence of AChE, Aβ, and THC, and Fo is the fluorescence of AChE and Aβ, was used to quantify the extent to which each compound inhibits Aβ aggregation. The student's t-test function of Microsoft Excel was used to determine p values and assess statistical significance between reactions.

Control experiments containing AChE, THC, and thioflavin T or AChE and thioflavin T alone were also performed to ensure that any observed fluorescence decrease was not attributable to the molecular rotor properties of thioflavin T upon binding to AChE. For these reactions, all concentrations were identical to those used in the described Aβ aggregation assays (vide supra).

Results and Discussion.

THC binding to AChE initially was modeled in silico using AutoDock 3.0.5.21 Twenty docking runs with 100 million energy evaluations each were performed with a 26.25 Å × 18.75 Å × 26.25 Å grid box with 0.375 Å grid spacing, which included regions of both the catalytic site and the PAS. Examination of the docking results revealed that THC was predicted to bind to AChE with comparable affinity to the best reported PAS binders, with the primary binding interaction observed between the ABC fused ring of the THC scaffold and the Trp86 indole side chain of AChE (Figure 2). Further interactions were also evident between THC and the backbone carbonyls of Phe123 and Ser125. Encouraged by these results, we tested the ability of THC to inhibit AChE catalytic activity. Steady-state kinetic analysis of THC inhibition revealed that THC competitively inhibits AChE (Ki = 10.2 μM) (Figure 3A). This level of inhibition is relatively modest, yet it is important to note that inhibition of acetylcholine cleavage is not a prerequisite for effective reduction of Aβ aggregation; indeed, most PAS binders are moderate AChE inhibitors displaying either non-competitive or mixed-type inhibition.16 While THC shows competitive inhibition relative to the substrate, this does not necessitate a direct interaction between THC and the AChE active site. In fact, given the proximity of the PAS to the protein channel leading to the catalytic triad active site, it is possible to block substrate entry into the active site while bound to the PAS, thus preventing the formation of an ESI complex.18,24 In order to test this hypothesis, additional kinetic experiments were performed to determine the mutual exclusivity of THC and propidium, a well characterized purely noncompetitive AChE inhibitor and PAS binder. Dixon plots of ν-1 versus propidium concentration at varying concentrations of THC returned a series of parallel lines, indicating that THC and propidium cannot bind simultaneously to AChE (Figure 3B). Thus, these studies verify our docking results and demonstrate that THC and propidium are mutually exclusive PAS inhibitors. Additionally, recent reports have suggested that the selectivity of a given inhibitor for AChE over butyrylcholinesterase (BuChE) can be correlated with the ability of a compound to block AChE-accelerated Aβ aggregation.25,26 Kinetic examination of BuChE inhibition revealed a slight reduction in enzymatic activity at high concentrations of THC (IC50 ≥ 100 μM); however, these experiments were limited by the poor solubility of THC in aqueous solution.


Predicted binding mode of THC (gray) to AChE (orange ribbon). The catalytic triad residues of AChE (green) and water molecules included in the docking calculations (light blue spheres) are shown.


(A) Kinetic analysis of AChE inhibition by 0.0 (●), 6.25 (▲), 12.5 (), and 25.0 μM (■) THC. Steady state kinetic analysis was performed using acetylthiocholine (75-300 μM) and Ellman's reagent (340 μ ...

The activity of THC towards the inhibition of Aβ aggregation was then investigated using a thioflavin T (ThT)-based fluorometric assay to stain putative Aβ fibrils.23 Using this assay, we found that THC is an effective inhibitor of the amyloidogenic effect of AChE (Figure 4). In fact, at a concentration of 50 μM, propidium does not fully prevent AChE-induced aggregation (p = 0.03, student's T-test), while THC completely blocks the AChE effect on Aβ aggregation, with significantly greater inhibition than propidium (p = 0.04, student's T-test), one of the most effective aggregation inhibitors reported to date.16 However, the observed decrease in fluorescence could also be rationalized as a result of a competition between THC and ThT for the same site on AChE. It has been shown that ThT also can bind to the PAS and that this binding leads to an increase in fluorescence. Presumably, this phenomenon results from ThT serving as a molecular rotor in which fluorescence quantum yield is sensitive to the intrinsic rotational relaxation; thus, when molecular rotation is slowed by protein binding, the quantum yield of the molecule can increase dramatically.27,28 In order to ensure that the observed fluorescence decrease was due to fibril inhibition, control experiments were performed using AChE, THC, and ThT. Reactions containing AChE and ThT alone showed the same fluorescence output as those containing AChE, THC, and ThT, providing convincing evidence that any observed reduction in fluorescence can be attributed to fewer Aβ fibrils.

Inhibition of AChE-induced Aβ aggregation by THC and propidium (* p < 0.05 versus Aβ only; # p < 0.05 versus Aβ + propidium).

Conclusion.

We have demonstrated that THC competitively inhibits AChE, and furthermore, binds to the AChE PAS and diminishes Aβ aggregation. In contrast to previous studies aimed at utilizing cannabinoids in Alzheimer's disease therapy,8-10 our results provide a mechanism whereby the THC molecule can directly impact Alzheimer's disease pathology. We note that while THC provides an interesting Alzheimer's disease drug lead, it is a psychoactive compound with strong affinity for endogenous cannabinoid receptors. It is noteworthy that THC is a considerably more effective inhibitor of AChE-induced Aβ deposition than the approved drugs for Alzheimer's disease treatment, donepezil and tacrine, which reduced Aβ aggregation by only 22% and 7%, respectively, at twice the concentration used in our studies.7 Therefore, AChE inhibitors such as THC and its analogues may provide an improved therapeutic for Alzheimer's disease, augmenting acetylcholine levels by preventing neurotransmitter degradation and reducing Aβ aggregation, thereby simultaneously treating both the symptoms and progression of Alzheimer's disease.



http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2562334/

 

[RetroGrow]

Good post. I wonder what the opponents of cannabis think when they read these type studies/results. Do they just dismiss it out of hand, or does it give them any pause to think at all?
How much proof of the healing effects of this most unique plant do they need, before the light exposes their ignorance and spitefulness?

 

[trichrider]

http://www.mapinc.org/drugnews/v05/n307/a10.html

STUDY: MARIJUANA SLOWS ALZHEIMER'S DECLINE

New Spanish and Israeli research shows that a synthetic analogue of the active component of marijuana can reduce the inflammation and prevent the mental decline associated with Alzheimer's disease. Although it was conducted on human brain tissue in the lab and in a rat model -- but not in living humans -- the research is regarded as a major step not only in understanding how the brain reacts to Alzheimer's disease, but also in helping to develop novel drugs for Alzheimer's and even Parkinson's disease.

Prof. Raphael Mechoulam, a medicinal chemistry expert who discovered marijuana's active component ( called THC ), conducted the study with researchers at the Cajal Institute and Complutense University in Madrid, led by Maria de Ceballos. The study appears in Wednesday's issue of The Journal of Neuroscience, which is published by the Society for Neuroscience, an organization of more than 36,000 basic scientists and clinicians who study the brain and nervous system.

To show the preventive effects of cannabinoids on Alzheimer's disease, the team first compared the brain tissue of patients who died from Alzheimer's disease with that of healthy people who had died at a similar age. They looked closely at cannabinoid receptors CB1 and CB2 - proteins to which cannabinoids bind, allowing their effects to be felt - and atmicroglia, which activate the brain s immune response. Micro-glia collect near plaques and, when active, cause inflammation. The researchers found a dramatically reduced functioning of cannabinoid receptors in diseased brain tissue, meaning that patients had lost the capacity to experience cannabinoids' protective effects.

In addition, the researchers showed that cannabinoids prevented cognitive decline through rat experiments. They injected either amyloid ( which leads to cognitive decline ) that had been allowed to aggregate or control proteins into the brains of rats for one week. Other rats were injected with a cannabinoid and either amyloid or a control protein. After two months, the researchers trained the rats over five days to find a platform hidden underwater. Rats treated with the control protein - with or without cannabinoids - and those treated with the amyloid protein and cannabinoid were able to find the platform. Rats treated with amyloid protein alone did not learn how to find the platform.

Meshoullam said that the discovery was important, since most drugs given for neurodegenerative diseases like Alzheimer's and Parkinson's are work merely against symptoms and not the cause and essence of the neurodegeneration. It is not necessary to smoke marijuana to conduct trials, but to use the synthetic versions of the active ingredient, he told The Jerusalem Post.

Clinical trials have not yet been scheduled or a request made for approval. It is very complicated and expensive to run clinical trials, he said, but he hoped they would be carried out due to the massive threat to human health of Alzheimer's and other neurodegenerative disorders.

The researchers found that the presence of amyloid protein in the rats' brains activated immune cells. Rats that received the control protein alone or cannabinoid and a control protein did not show activation of microglia. Using cell cultures, the investigators confirmed that cannabinoids counteracted the activation of microglia and thus reduced inflammation. These findings that cannabinoids work both to prevent inflammation and to protect the brain may set the stage for their use as a therapeutic approach for Alzheimer's disease, de Ceballos said. The scientists will now focus their efforts on targeting one of the two main cannabinoid receptors that is not involved in producing the psychotropic effects, or high, from marijuana.

 

[trichrider]

Prevention of Alzheimer's Disease Pathology by Cannabinoids: Neuroprotection Mediated by Blockade of Microglial Activation

Belén G. Ramírez1,
Cristina Blázquez2,
Teresa Gómez del Pulgar2,
Manuel Guzmán2, and
María L. de Ceballos1

The Journal of Neuroscience, 23 February 2005, 25(8): 1904-1913; doi: 10.1523/JNEUROSCI.4540-04.2005

Abstract
Full Text
Full Text (PDF)


Abstract

Alzheimer's disease (AD) is characterized by enhanced β-amyloid peptide (βA) deposition along with glial activation in senile plaques, selective neuronal loss, and cognitive deficits. Cannabinoids are neuroprotective agents against excitotoxicity in vitro and acute brain damage in vivo. This background prompted us to study the localization, expression, and function of cannabinoid receptors in AD and the possible protective role of cannabinoids after βA treatment, both in vivo and in vitro. Here, we show that senile plaques in AD patients express cannabinoid receptors CB1 and CB2, together with markers of microglial activation, and that CB1-positive neurons, present in high numbers in control cases, are greatly reduced in areas of microglial activation. In pharmacological experiments, we found that G-protein coupling and CB1 receptor protein expression are markedly decreased in AD brains. Additionally, in AD brains, protein nitration is increased, and, more specifically, CB1 and CB2 proteins show enhanced nitration. Intracerebroventricular administration of the synthetic cannabinoid WIN55,212-2 to rats prevent βA-induced microglial activation, cognitive impairment, and loss of neuronal markers. Cannabinoids (HU-210, WIN55,212-2, and JWH-133) block βA-induced activation of cultured microglial cells, as judged by mitochondrial activity, cell morphology, and tumor necrosis factor-α release; these effects are independent of the antioxidant action of cannabinoid compounds and are also exerted by a CB2-selective agonist. Moreover, cannabinoids abrogate microglia-mediated neurotoxicity after βA addition to rat cortical cocultures. Our results indicate that cannabinoid receptors are important in the pathology of AD and that cannabinoids succeed in preventing the neurodegenerative process occurring in the disease.

http://www.jneurosci.org/content/25/8/1904.abstract

 

[unregistered190]

Bookmarked so I can come back and read when I have time! Interesting

 

[trichrider]

http://norml.org/library/item/alzheimer-s-disease

Alzheimer's Disease




Alzheimer's disease (AD) is a neurological disorder of unknown origin that is characterized by a progressive loss of memory and learned behavior. Patients with Alzheimer's are also likely to experience depression, agitation and appetite loss, among other symptoms. Over 4.5 million Americans are estimated to be afflicted with the disease. No approved treatments or medications are available to stop the progression of AD, and few pharmaceuticals have been FDA-approved to treat symptoms of the disease.

A review of the recent scientific literature indicates that cannabinoid therapy may provide symptomatic relief to patients afflicted with AD while also moderating the progression of the disease.

Writing in the February 2005 issue of the Journal of Neuroscience, investigators at Madrid's Complutense University and the Cajal Institute in Spain reported that the intracerebroventricular administration of the synthetic cannabinoid WIN 55,212-2 prevented cognitive impairment and decreased neurotoxicity in rats injected with amyloid-beta peptide (a protein believed to induce Alzheimer's). Additional synthetic cannabinoids were also found to reduce the inflammation associated with Alzheimer's disease in human brain tissue in culture. "Our results indicate that ... cannabinoids succeed in preventing the neurodegenerative process occurring in the disease," investigators concluded.[1] Follow up studies by investigators demonstrated that the administration of the nonpsychotropic plant cannabinoid cannabidiol (CBD) also mitigated memory loss in a mouse model of the disease.[2]

Investigators at The Scripps Research Institute in California in 2006 reported that THC inhibits the enzyme responsible for the aggregation of amyloid plaque — the primary marker for Alzheimer's disease — in a manner "considerably superior" to approved Alzheimer's drugs such as donepezil and tacrine. "Our results provide a mechanism whereby the THC molecule can directly impact Alzheimer's disease pathology," researchers concluded. "THC and its analogues may provide an improved therapeutic [option] for Alzheimer's disease [by]... simultaneously treating both the symptoms and the progression of [the] disease."[3]

More recently, investigators at Ohio State University, Department of Psychology and Neuroscience, reported that older rats administered daily doses of WIN 55,212-2 for a period of three weeks performed significantly better than non-treated controls on a water-maze memory test. Writing in the journal Neuroscience in 2007, researchers reported that rats treated with the compound experienced a 50 percent improvement in memory and a 40 to 50 percent reduction in inflammation compared to controls.[4]

Previous preclinical studies have demonstrated that cannabinoids can prevent cell death by anti-oxidation.[5] Some experts believe that cannabinoids' neuroprotective properties could also play a role in moderating AD.[6] Writing in the September 2007 issue of the British Journal of Pharmacology, investigators at Ireland's Trinity College Institute of Neuroscience concluded, "[C]annabinoids 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. ... Manipulation of the cannabinoid pathway offers a pharmacological approach for the treatment of AD that may be efficacious than current treatment regimens."[7]

In addition to potentially modifying the progression of AD, clinical trials also indicate that cannabinoid therapy can reduce agitation and stimulate weight gain in patients with the disease. Most recently, investigators at Berlin Germany's Charite Universitatmedizin, Department of Psychiatry and Psychotherapy, reported that the daily administration of 2.5 mg of synthetic THC over a two-week period reduced nocturnal motor activity and agitation in AD patients in an open-label pilot study.[8]

Clinical data presented at the 2003 annual meeting of the International Psychogeriatric Association previously reported that the oral administration of up to 10 mg of synthetic THC reduced agitation and stimulated weight gain in late-stage Alzheimer's patients in an open-label clinical trial.[9] Improved weight gain and a decrease in negative feelings among AD patients administered cannabinoids were previously reported by investigators in the International Journal of Geriatric Psychiatry in 1997.[10]

 

[trichrider]

http://www.dailymail.co.uk/health/article-1332760/Alzheimers-risk-rises-mother-sufferer.html

Alzheimer's 'risk rises if your mother was a sufferer'

Researchers found those whose mothers were diagnosed with Alzheimer's could be at greater risk of developing the disease (file picture)


Anyone whose mother had Alzheimer’s could be at greater risk of developing it than if their father had the disease, warn researchers.


Those with a family history of Alzheimer’s are known to be at significantly higher risk of being diagnosed with the illness themselves.


But for the first time a study has suggested that the likelihood of it being passed on can depend on which parent was affected.


Researchers found that those whose mothers were diagnosed with the disease had altered levels of the protein amyloid – which plays a part in its development.


In addition, they had higher levels of proteins involved with oxidative stress, which can damage cells in the brain.


In contrast, those whose fathers had Alzheimer’s and those with no family history had protein levels within normal ranges.


Dr Lisa Mosconi, of the New York University School of Medicine, who carried out the research, said: ‘Our data indicate that adult children of mothers with Alzheimer’s may be at increased risk of developing the disease. It is therefore extremely important to understand the genetic mechanisms involved in maternal transmission, which are currently unknown.


‘Identifying a genetic predictor for the disease might lead to preventive treatments years before the onset of clinical symptoms.’




More...
Cocktail of cheap drugs 'can prevent Alzheimer's' and keep the brain healthy into old age


Alzheimer’s and other forms of dementia, which cause shrinkage of the brain, affect more than 700,000 people in the UK.


Alzheimer’s disease, the most common form of dementia, leads to a progressive loss of memory and thinking ability.


The study, published in the Biological Psychiatry journal, looked at genomic imprinting, where the pattern of the inherited disease differs based on whether the risk genes are inherited from the mother or the father.


The journal’s editor, Dr John Krystal, said: ‘In theory, some day, one might develop a medication that reduces the risks associated with a maternal history of Alzheimer’s disease.’

 

[mexcurandero420]

Elevated Serum Pesticide Levels and Risk for Alzheimer Disease

Keep on growing

 

[trichrider]

What Do You Want to Know About Alzheimer's Disease?

http://www.healthline.com/health/alzheimers-disease

 

[trichrider]

Researchers find five new Alzheimer's genes

http://usatoday30.usatoday.com/news...ers-New-genes-linked-to-Alzheimers/45715102/1

 

[trichrider]

http://www.sciencedaily.com/releases/2007/10/071014163644.htm

Cannabis Use, Effect And Potential Therapy For Alzheimer's, MS and Parkinson's


Date:

October 15, 2007


Source:

European College of Neuropsychopharmacology


Summary:


Cannabis (marijuana) is the most widely produced plant-based illicit drug worldwide and the illegal drug most frequently used in Europe. Its use increased in almost all EU countries during the 1990s, in particular among young people, including school students. Cannabis use is highest among 15- to 24-year-olds, with lifetime prevalence ranging for most countries from 20 -- 40%. Recently there has been a new surge in the level of concern about potential social and health outcomes of cannabis use, although the available evidence still does not provide a clear-cut understanding of the issues.

 

[trichrider]

http://www.jneurosci.org/content/25/8/1904.abstract

Abstract

Alzheimer's disease (AD) is characterized by enhanced β-amyloid peptide (βA) deposition along with glial activation in senile plaques, selective neuronal loss, and cognitive deficits. Cannabinoids are neuroprotective agents against excitotoxicity in vitro and acute brain damage in vivo. This background prompted us to study the localization, expression, and function of cannabinoid receptors in AD and the possible protective role of cannabinoids after βA treatment, both in vivo and in vitro. Here, we show that senile plaques in AD patients express cannabinoid receptors CB1 and CB2, together with markers of microglial activation, and that CB1-positive neurons, present in high numbers in control cases, are greatly reduced in areas of microglial activation. In pharmacological experiments, we found that G-protein coupling and CB1 receptor protein expression are markedly decreased in AD brains. Additionally, in AD brains, protein nitration is increased, and, more specifically, CB1 and CB2 proteins show enhanced nitration. Intracerebroventricular administration of the synthetic cannabinoid WIN55,212-2 to rats prevent βA-induced microglial activation, cognitive impairment, and loss of neuronal markers. Cannabinoids (HU-210, WIN55,212-2, and JWH-133) block βA-induced activation of cultured microglial cells, as judged by mitochondrial activity, cell morphology, and tumor necrosis factor-α release; these effects are independent of the antioxidant action of cannabinoid compounds and are also exerted by a CB2-selective agonist. Moreover, cannabinoids abrogate microglia-mediated neurotoxicity after βA addition to rat cortical cocultures. Our results indicate that cannabinoid receptors are important in the pathology of AD and that cannabinoids succeed in preventing the neurodegenerative process occurring in the disease.

 

[trichrider]

http://www.sciencedirect.com/science/article/pii/S104474311300064X

Role of the cannabinoid system in the transit of beta-amyloid across the blood–brain barrier

 

[trichrider]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2562334/

Abstract.


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 as well as reduce the health care costs attributable to Alzheimer's disease. Here, we demonstrate that the active component of marijuana, Δ9-tetrahydrocannabinol (THC), competitively inhibits the enzyme acetylcholinesterase (AChE) as well as prevents AChE-induced amyloid β-peptide (Aβ) 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 Aβ aggregation, and this study provides a previously unrecognized molecular mechanism through which cannabinoid molecules may directly impact the progression of this debilitating disease.