www.perpetualcommotion.com
"Give with a free hand, but give only your own."
 -- J.R.R. Tolkien The Children of Hurin
- The Distillery -


(In other words, "I found it interesting, but haven't had the time to research and catagorize it yet.")


(Source: Medscape) - Poor dental health has been linked to an increased risk for dementia, new research shows.

In a study of more than 4000 elderly adults in Japan, those who had few teeth and who did not use dentures or who did not visit a dentist regularly had a significantly higher risk for dementia onset than the participants who practiced better dental health practices...
http://r20.rs6.net/tn.jsp?e=001NJkHqF6BqziZqEtbJhoHGVUsG1vnQuEzFeCQiPaoA32MSt-J_NlLnAvqEFKoZ6a8x-rVR4m4ExcKivyITNg67fxSZCwvjPuetl_qm1oSoZv6VHBJHEVcqWr3lmaatDK5TeHzLUCHx2I=

A Combination of Green Tea Extract and l-Theanine Improves Memory and Attention in Subjects with Mild Cognitive Impairment: A Double-Blind Placebo-Controlled Study

Journal of Medicinal Food
Published in Volume: 14 Issue 4: March 28, 2011

Abstract
A combination of green tea extract and l-theanine (LGNC-07) has been reported to have beneficial effects on cognition in animal studies.
http://online.liebertpub.com/doi/abs/10.1089/jmf.2009.1374
http://www.alzconnected.org/discussion.aspx?g=posts&t=2147487244

...at amazon.com and elsewhere it's easy to buy capsules of green tea extract + L-theanine, though I don't know how their potency compares to what was successful in the above study.  And I don't yet know possible side-effects...

Also note that L-Theanine should not be confused with L-Threonate

(LG Household and Health Care Ltd.)

http://www.nutraingredients-usa.com/Research/Green-tea-extract-shows-memory-boosting-activity-Study

...when he gave his relative glucuronolactone powder in combination with theanine she became more alert and her behavior improved (the theanine by itself was not particularly effective).  A metabolite of glucuronolactone--glucaric acid--is found in apple juice (although the sugar in the juice may be somewhat of a problem).  Apple juice like green tea has been suggested as a way to delay the onset of Alzheimer's disease and as a possible treatment for Alzheimer's disease especially during its early stages.  
http://www.eurekalert.org/pub_releases/2009-01/ip-nsp012209.php
http://www.ncbi.nlm.nih.gov/pubmed/20338990

It turns out that the same toxin (peroxynitrite) that probably causes damage to the brain in Alzheimer's disease also damages the brain as a result of a stroke.

http://www.jneurosci.org/content/19/14/5910.short
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1865248/

Various essential oils protect the brain in four ways: they limit the formation of peroxynitrites, they lower levels of peroxynitrites, they inhibit peroxynitrite-mediated damage, and they partially reverse the damage done by peroxynitrites.  In essence, they limit the damage done to the brain by stroke and Alzheimer's disease.
See also"aromatherapy in the treatment of Alzheimer's disease" http://www.alzconnected.org/discussion.aspx?g=posts&t=2147484055
 
The following article is from The Vitamin D Council:

http://blog.vitamindcouncil.org/2012/04/23/dietary-vitamin-d-intake-and-sun-exposure-linked-to-lower-risk-of-alzheimers-in-france/

Dietary vitamin D intake and sun exposure linked to lower risk of Alzheimer’s in France
 
Posted on April 23, 2012 by Dr. William Grant

A paper published ahead of print on April 13 found that consumption of vitamin D-rich foods and midday sun exposure were associated with significantly reduced risk of developing Alzheimer’s disease [Annweiler et al., 2012]. The study was an add-on to the Epidemiology of Osteoporosis (EPIDOS) Toulouse cohort study at 43.6º N.

 Annweiler C, et al. Higher vitamin D dietary intake is associated with lower risk of Alzheimer’s disease: A 7-year follow-up. J Gerontol A Biol Sci Med Sci. 2012 Apr 13.

This cohort included women over the age of 75 years at time of enrollment and was designed to study risk factors for hip fractures over a four-year period. Women who had taken vitamin D supplements in the 18 months prior to enrollment were excluded. Dietary factors and midday sun exposure habits were examined at time of enrollment. The mean dietary vitamin D intake was 334±172 IU/day. The presence of Alzheimer’s disease and other dementias was assessed seven years after enrollment.

Those in the highest fifth of vitamin D intake had one-quarter the incidence rate of Alzheimer’s disease as the other four fifths [odds ratio (OR) = 0.23 (95% confidence interval (CI), 0.08-0.69)]. In addition, those in the highest fifth of sun exposure had half the incidence rate of Alzheimer’s disease [OR = 0.45 (95% CI, 0.24-0.85)]. Neither dietary vitamin D intake nor sun exposure was significantly associated with risk of other dementia.

As mentioned in the paper, there is a considerable body of literature reporting that fish consumption is associated with reduced risk of Alzheimer’s disease, with the usual reason given that fish is an important dietary source of omega-3 fatty acids. This finding was likely first reported in an ecological study in 1997 [Grant, 1997]. Thus, it is not clear from the present study how much of the reduced risk of Alzheimer’s disease was due to omega-3 fatty acids and how much to vitamin D.

However, the finding regarding sun exposure at midday strongly supports the role of vitamin D in reducing risk. Casual sun exposure in England for those aged 45 years is sufficient to increase serum 25-hydroxyvitamin D concentrations by 38 nmol/l (15 ng/ml) [Hyppönen and Power, 2007]. This increase is equivalent to about 1500-2000 IU/day [Garland, 2011]. However, for those over the age of 75 years, vitamin D production rates would be less, perhaps one-half as much [MacLaughlin and Holick, 1985].

Thus, this study provides good evidence that fish consumption and midday sun exposure reduce the risk of Alzheimer’s disease, with vitamin D being the likely agent. The neuroprotective actions of vitamin D are discussed in the paper by Annweiler et al.

References

Annweiler C, Rolland Y, Schott AM, Blain H, Vellas B, Herrmann FR, Beauchet O. Higher vitamin D dietary intake is associated with lower risk of Alzheimer’s disease: A 7-year follow-up. J Gerontol A Biol Sci Med Sci. 2012 Apr 13. [Epub ahead of print]

Garland CF, French CB, Baggerly LL, Heaney RP. Vitamin D supplement doses and serum 25-hydroxyvitamin D in the range associated with cancer prevention. Anticancer Res 2011:31: 617-22.

Grant WB. Dietary links to Alzheimer’s disease. Alz Dis Rev 1997;2:42-55. (http://www.sunarc.org/JAD97.pdf)

Hyppönen E, Power C. Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors. Am J Clin Nutr. 2007 Mar;85(3):860-8.

MacLaughlin J, Holick MF. Aging decreases the capacity of human skin to produce vitamin D3. J Clin Invest. 1985 Oct;76(4):1536-8.

Study Dusts Sugar Coating Off Little-Known Regulation in Cells

ScienceDaily (Apr. 16, 2012) — In Alzheimer's disease, brain neurons become clogged with tangled proteins. Scientists suspect these tangles arise partly due to malfunctions in a little-known regulatory system within cells. Now, researchers have dramatically increased what they know about this particular regulatory system in mice. Such information will help scientists better understand Alzheimer's and other diseases in humans and could eventually provide new targets for therapies... The O-GlcNAc system likely adds another layer of control to the proteins that serve as a brain cell's widgets and gears -- control that might be muddled in Alzheimer's brains known to have problems in sugar metabolism...
http://www.sciencedaily.com/releases/2012/04/120416154048.htm

Epo-D About a year ago in the Alzheimer's Research Forum reported:

"In a study performed on three-month-old mice with tauopathy, one of these compounds, epothilone D, when given at the relatively low dose of 1 mg/kg body weight for three months, decreased axon degeneration and improved cognition in treated animals (see Brunden et al., 2010). [ NEED LINK ]

This month, in the Journal of Neuroscience, Brunden and his colleagues report positive results in older tauopathy mice using 1/30th to 1/100th of the dose used with cancer patients. Here is the website for the original press release http://www.uphs.upenn.edu/news/News_Releases/2012/03/alzheimer/ This drug is now in human trials with Alzheimer's patients that ends in 2014.

Methylene Blue/2nd gen Rember. TauRx.com's website states: "…the clinical tolerability profile of LMTX, one of TauRx's second generation TAIs, is currently being investigated clinically in trials conducted under an open US IND. TauRx is now preparing to advance LMTX into pivotal international phase 3 trials in mild and moderate AD and related neurodegenerative diseases." [ NEED TO FIND LINK ]

In the meantime, two OTC low toxicity agents with established neuroprotective and neuro-repair properties merit review: bio-available curcumin (Longvida) and a new product that comes from research done at the Salk Institute, fisetin (Swanson). Both are strong anti-oxidants and anti-inflammatories that protect and help neurons repair damage from tauopathy.

San Francisco: Tau—Time to Shine as Therapeutic Target?
17 May 2011. At the “Tau and Tauopathies: Pathogenic Mechanisms” workshop held 28-30 March 2011 at the Gladstone Institute of Neurological Disease (GIND) in San Francisco... The researchers found that tau pathology correlated with increased serum IL-1β in the transgenic mice, and wondered whether blocking signals through this inflammatory cytokine could possibly help... epothilone D—a brain-penetrant, microtubule-stabilizing compound that slowed axon degeneration and improved cognition... hyperphosphorylated tau... “If you express c-Abl in the forebrain, you get tau phosphorylation, cell death, and gliosis accompanying the cell loss,”... The results are reminiscent of the cognitive recovery seen in tangle-bearing Tg4510 mice after tau transgene inhibition with doxycycline (ARF related news story on Santacruz et al., 2005), Cole wrote in an e-mail to ARF. The data “support tau oligomers as a target and curcumin as a pleiotropic drug capable of targeting pure tauopathy with late intervention,” he noted. Investigators at Jaslok Hospital and Research Centre in Mumbai, India, are recruiting AD patients for a Phase 2 trial of a highly absorbed, lipophilic curcumin formulation. Manufactured as a food supplement called LongVida by Verdure Sciences... eight-week treatment with the autophagy-promoting compound trehalose cleared tau aggregates and improved behavior in tauopathy mouse models with primarily motor...
http://www.alzforum.org/new/detail.asp?id=2792


This excerpt is from a 2010 case description (LaBuzetta, et.al. 2010):

"Signs and symptoms of hyperammonemia are usually neurological in nature and range from mild cognitive and psychomotor changes to impaired intellectual functioning, personality changes, altered levels of consciousness, and neuromuscular dysfunction. At high enough concentrations, coma or death can be observed."

New findings contradict dominant theory in Alzheimer’s disease

28 October 2011

For decades the amyloid hypothesis has dominated the research field in Alzheimer’s disease. The theory describes how an increase in secreted beta-amyloid peptides leads to the formation of plaques, toxic clusters of damaged proteins between cells, which eventually result in neurodegeneration. Scientists at Lund University, Sweden, have now presented a study that turns this premise on its head. The research group’s data offers an opposite hypothesis, suggesting that it is in fact the neurons’ inability to secrete beta-amyloid that is at the heart of pathogenesis in Alzheimer’s disease...
http://www.lunduniversity.lu.se/o.o.i.s?id=24890&news_item=5718

Clearance of beta amyloid accumulation within neurons stops memory decline

the UCI research team is the first to identify that early beta amyloid accumulation within neurons is the trigger for the onset of memory decline in Alzheimer's.
"This finding has important and useful implications for the pharmaceutical industry in terms of developing drugs that can target beta amyloid as soon as it accumulates within the neurons," said Frank LaFerla, principal investigator of the research project, associate professor of neurobiology and behavior, and co-director of the UCI Institute for Brain Aging and Dementia. "Once the plaques and tangles form, it is too late."

http://www.news-medical.net/news/2005/03/06/8174.aspx



Impaired β-Amyloid Secretion in Alzheimer's Disease Pathogenesis

Davide Tampellini, Nawreen Rahman, Michael T. Lin, Estibaliz Capetillo-Zarate1, and Gunnar K. Gouras

Abstract

A central question in Alzheimer's disease (AD) research is what role β-amyloid peptide (Aβ) plays in synaptic dysfunction. Synaptic activity increases Aβ secretion, potentially inhibiting synapses, but also decreases intraneuronal Aβ, protecting synapses. We now show that levels of secreted Aβ fall with time in culture in neurons of AD-transgenic mice, but not wild-type mice. Moreover, the ability of synaptic activity to elevate secreted Aβ and reduce intraneuronal Aβ becomes impaired in AD-transgenic but not wild-type neurons with time in culture. We demonstrate that synaptic activity promotes an increase in the Aβ-degrading protease neprilysin at the cell surface and a concomitant increase in colocalization with Aβ42. Remarkably, AD-transgenic but not wild-type neurons show reduced levels of neprilysin with time in culture. This impaired ability to secrete Aβ and reduce intraneuronal Aβ has important implications for the pathogenesis and treatment of AD.
http://www.jneurosci.org/content/31/43/15384.abstract



Human Cytomegalovirus
Essential hypertension:

Virus can cause high blood pressure
2011/08/15

BEIJING: High blood pressure could be caused by a common virus, according to a study carried out by a team of Chinese doctors which has possible implications for millions of people around the world.


The human cytomegalovirus (HCMV) infects most adults but is repressed by the body’s immune system and rarely causes any symptoms.

But a team from Beijing Chaoyang Hospital’s cardiology centre has found the first evidence of a link between HCMV and essential hypertension, according to a report published on the website of the US medical journal Circulation.
http://www.nst.com.my/nst/articles/Viruscancausehighbloodpressure/Article/


Virus can cause high blood pressure: Chinese study
Agence France-Presse
Posted at 08/15/2011
http://www.abs-cbnnews.com/lifestyle/08/15/11/virus-can-cause-high-blood-pressure-chinese-study

Virus can cause high blood pressure: Chinese study
Relaxnews – Wed, Aug 17, 2011
http://news.yahoo.com/virus-cause-high-blood-pressure-chinese-study-153649965.html


Virus can cause high blood pressure: Chinese study
AFP NewsBy Philip Lim | AFP News – Mon, Aug 15, 2011
http://my.news.yahoo.com/virus-cause-high-blood-pressure-chinese-study-095735139.html


Treatment With Vitamin C Dissolves Toxic Protein Aggregates in Alzheimer's Disease
ScienceDaily (Aug. 18, 2011)
 — Researchers at Lund University have discovered a new function for vitamin C. Treatment with vitamin C can dissolve the toxic protein aggregates that build up in the brain in Alzheimer's disease...
http://www.sciencedaily.com/releases/2011/08/110818101645.htm

What form of vitamin C?  How much?  Is it practical for someone to take orally?


Fish Oil's Impact On Cognition and Brain Structure Identified in New Study
ScienceDaily (Aug. 17, 2011)
 — Researchers at Rhode Island Hospital's Alzheimer's Disease and Memory Disorders Center have found positive associations between fish oil supplements and cognitive functioning as well as differences in brain structure between users and non-users of fish oil supplements. The findings suggest possible benefits of fish oil supplements on brain health and aging...
http://www.sciencedaily.com/releases/2011/08/110817120220.htm

Exercise May Help Prevent Brain Damage Caused by Alzheimer's Disease
ScienceDaily (Aug. 15, 2011)
 — Regular exercise could help prevent brain damage associated with neurodegenerative diseases like Alzheimer's, according to research published this month in Elsevier's journal Brain, Behavior, and Immunity...
http://www.sciencedaily.com/news/mind_brain/alzheimer%27s/

Moderate Drinking May Protect Against Alzheimer's and Cognitive Impairment, Study Suggests
ScienceDaily (Aug. 15, 2011)
 — Moderate social drinking may significantly reduce the risk of dementia and cognitive impairment, suggests an analysis of 143 studies by Loyola University Chicago Stritch School of Medicine researchers...
http://www.sciencedaily.com/releases/2011/08/110816112134.htm

Red wine and resveratrol?

Alzheimer's disease - a neurospirochetosis. Analysis of the evidence following Koch's and Hill's criteria.

Judith Miklossy

Correspondence: Judith Miklossy judithmiklossy@bluewin.ch
Journal of Neuroinflammation 2011, 8:90 doi:10.1186/1742-2094-8-90

Published: 4 August 2011

Abstract (provisional)

It is established that chronic spirochetal infection can cause slowly progressive dementia, brain atrophy and amyloid deposition in late neurosyphilis.

Recently it has been suggested that various types of spirochetes, in an analogous way to Treponema pallidum, could cause dementia and may be involved in the pathogenesis of Alzheimer's disease (AD).

Here, we review all data available in the literature on the detection of spirochetes in AD and critically analyze the association and causal relationship between spirochetes and AD following established criteria of Koch and Hill.

The results show a statistically significant association between spirochetes and AD (P = 1.5 x 10-17, OR = 20, 95% CI = 8-60, N = 247).

When neutral techniques recognizing all types of spirochetes were used, or the highly prevalent periodontal pathogen Treponemas were analyzed, spirochetes were observed in the brain in more than 90% of AD cases.

Borrelia burgdorferi was detected in the brain in 25.3% of AD cases analyzed and was 13 times more frequent in AD compared to controls.

Periodontal pathogen Treponemas (T. pectinovorum, T. amylovorum, T. lecithinolyticum, T. maltophilum, T. medium, T. socranskii) and Borrelia burgdorferi were detected using species specific PCR and antibodies.

Importantly, co-infection with several spirochetes occurs in AD.

The pathological and biological hallmarks of AD were reproduced in vitro.

The analysis of reviewed data following Koch's and Hill's postulates shows a probable causal relationship between neurospirochetosis and AD.

Persisting inflammation and amyloid deposition initiated and sustained by chronic spirochetal infection form together with the various hypotheses suggested to play a role in the pathogenesis of AD a comprehensive entity.

As suggested by Hill, once the probability of a causal relationship is established prompt action is needed.

Support and attention should be given to this field of AD research.

Spirochetal infection occurs years or decades before the manifestation of dementia.

As adequate antibiotic and anti-inflammatory therapies are available, as in syphilis, one might prevent and eradicate dementia.

...

Conclusion

Various types of spirochetes, including B. burgdorferi, and six periodontal pathogen spirochetes ((T. socranskii, T. pectinovorum, T. denticola, T. medium, T. amylovorum and T. maltophilum) were detected in the brains of AD patients.

The pathological and biological hallmarks of AD, including increased AβPP level, Aβ deposition and tau phosphorylation were induced by spirochetes in vitro.

The statistical analysis showed a significant association between spirochetes and AD. The strongly significant association, the high risk factor and the analysis of data following Koch’s and Hill’s criteria, are indicative of a causal relationship between neurospirochetoses and AD.

Spirochetes are able to escape destruction by the host immune reactions and establish chronic infection and sustained inflammation.

In vivo studies with long exposure times will be necessary to efficiently study the sequence of events and the cellular mechanisms involved in spirochete induced AD-type host reactions and Aβ-plaque, “tangle” and “granulovacuolar” formation.

The characterization of all types of spirochetes and co-infecting bacteria and viruses is needed, in order to develop serological tests for the early detection of infection.

The pathological process is thought to begin long before the diagnosis of dementia is made therefore, an appropriate targeted treatment should start early in order to prevent dementia.

Persisting spirochetal infection and their persisting toxic components can initiate and sustain chronic inflammatory processes through the activation of the innate and adaptive immune system involving various signaling pathways.

In the affected brain the pathogens and their toxic components can be observed, along with host immunological responses.

The response itself is characteristic of chronic inflammatory processes associated with the site of tissue damage.

The outcome of infection is determined by the genetic predisposition of the patient, by the virulence and biology of the infecting agent
and by various environmental factors, such as exercise, stress and nutrition.

The accumulated knowledge, the various views, and hypotheses proposed to explain the pathogenesis of AD form together a comprehensive entity when observed in the light of a persisting chronic inflammation and amyloid deposition initiated and sustained by chronic spirochetal infection.

As suggested by Hill, once the probability of a causal relationship is established prompt action is needed. Similarly to syphilis, one may prevent and eradicate dementia in AD.

The impact on healthcare costs and on the suffering of the patients would be substantial.
http://www.jneuroinflammation.com/content/8/1/90/abstract
http://www.jneuroinflammation.com/content/pdf/1742-2094-8-90.pdf
J Neuroinflammation. 2011 Aug 4;8(1):90. [Epub ahead of print]
Alzheimer's disease - a neurospirochetosis. Analysis of the evidence following Koch's and Hill's criteria.
Miklossy J.
Abstract

ABSTRACT: It is established that chronic spirochetal infection can cause slowly progressive dementia, brain atrophy and amyloid deposition in late neurosyphilis. Recently it has been suggested that various types of spirochetes, in an analogous way to Treponema pallidum, could cause dementia and may be involved in the pathogenesis of Alzheimer's disease (AD). Here, we review all data available in the literature on the detection of spirochetes in AD and critically analyze the association and causal relationship between spirochetes and AD following established criteria of Koch and Hill. The results show a statistically significant association between spirochetes and AD (P = 1.5 x 10-17, OR = 20, 95% CI = 8-60, N = 247). When neutral techniques recognizing all types of spirochetes were used, or the highly prevalent periodontal pathogen Treponemas were analyzed, spirochetes were observed in the brain in more than 90% of AD cases. Borrelia burgdorferi was detected in the brain in 25.3% of AD cases analyzed and was 13 times more frequent in AD compared to controls. Periodontal pathogen Treponemas (T. pectinovorum, T. amylovorum, T. lecithinolyticum, T. maltophilum, T. medium, T. socranskii) and Borrelia burgdorferi were detected using species specific PCR and antibodies. Importantly, co-infection with several spirochetes occurs in AD. The pathological and biological hallmarks of AD were reproduced in vitro. The analysis of reviewed data following Koch's and Hill's postulates shows a probable causal relationship between neurospirochetosis and AD. Persisting inflammation and amyloid deposition initiated and sustained by chronic spirochetal infection form together with the various hypotheses suggested to play a role in the pathogenesis of AD a comprehensive entity. As suggested by Hill, once the probability of a causal relationship is established prompt action is needed. Support and attention should be given to this field of AD research. Spirochetal infection occurs years or decades before the manifestation of dementia. As adequate antibiotic and anti-inflammatory therapies are available, as in syphilis, one might prevent and eradicate dementia.

PMID: 21816039 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/21816039


Vitamin B12 status and rate of brain volume loss in community-dwelling elderly
doi: 10.1212/01.wnl.0000325581.26991.f2 Neurology September 9, 2008 vol. 71 no. 11 826-832
Conclusion: Low vitamin B12 status should be further investigated as a modifiable cause of brain atrophy and of likely subsequent cognitive impairment in the elderly.
http://www.neurology.org/content/71/11/826.abstract

Vitamin B clue to dementia
Thursday September 9 2010
NHS News (UK)
“Vitamin B tablets could slow and even halt the devastating march of Alzheimer's disease,” The Daily Telegraph reported. According to the newspaper, large daily doses of vitamin B can halve the rate of brain shrinkage, a process that can precede Alzheimer’s disease and dementia.
http://www.nhs.uk/news/2010/09September/Pages/vitamin-B12-brain-shrink-dementia.aspx



AD and dental work
http://alzheimers.infopop.cc/eve/forums/a/tpc/f/762104261/m/3194074997

Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation
First published July 27, 2011, doi: 10.3945/​ajcn.110.003483 Am J Clin Nutr September 2011 ajcn.003483
http://www.ajcn.org/content/early/2011/07/27/ajcn.110.003483.abstract#fn-2

Seeing the Data with New Eyes
The data suggest that it is time to redefine the clinical diagnosis of corticobasal degeneration
The UCSF Memory and Aging Center
http://us1.campaign-archive1.com/?u=d9019380fd1207ff3cec24450&id=742c689de9

Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders
Nature Reviews Neuroscience | AOP, published online 8 August 2007; doi:10.1038/nrn2194
http://neuro.pathology.pitt.edu/webstuff/Journal%20Club/tau%20review.pdf

SARASOTA - A blood-pressure drug found by the Roskamp Institute to show promise for arresting Alzheimer's disease has been approved for a five-year, $8.4 million Phase III human trial in Europe.

A Phase III clinical trial, which comes after studies on safety in human patients, is usually the last stop on a drug's long journey to market. The few medicines available for Alzheimer's merely address symptoms that result from this progressive brain disease. Just a handful that target suspected causes — like the Roskamp drug, Nilvadipine — have made it as far as Phase III, required for approval by the U.S. Food and Drug Administration.

http://www.heraldtribune.com/article/20110525/ARTICLE/110529725

http://www.rfdn.org/news_release_052511.html

April 23, 2010

Reduction of β-amyloid pathology by celastrol in a transgenic mouse model of Alzheimer’s disease

Filed under: alzheimer — Tags: Alzheimers disease, amyloid, Celastrol — admin @ 2:59 pm

Daniel Paris, Nowell J Ganey, Vincent Laporte, Nikunj S Patel, David Beaulieu-Abdelahad, Corbin Bachmeier, Amelia March, Ghania Ait-Ghezala and Michael J Mullan

The Roskamp Institute, 2040 Whitfield Avenue, Sarasota, FL 34243, USA

Journal of Neuroinflammation 2010, 7:17doi:10.1186/1742-2094-7-17

Published: 8 March 2010

Abstract

Background

Aβ deposits represent a neuropathological hallmark of Alzheimer’s disease (AD). Both soluble and insoluble Aβ species are considered to be responsible for initiating the pathological cascade that eventually leads to AD. Therefore, the identification of therapeutic approaches that can lower Aβ production or accumulation remains a priority. NFκB has been shown to regulate BACE-1 expression level, the rate limiting enzyme responsible for the production of Aβ. We therefore explored whether the known NFκB inhibitor celastrol could represent a suitable compound for decreasing Aβ production and accumulation in vivo.

Methods

The effect of celastrol on amyloid precursor protein (APP) processing, Aβ production and NFκB activation was investigated by western blotting and ELISAs using a cell line overexpressing APP. The impact of celastrol on brain Aβ accumulation was tested in a transgenic mouse model of AD overexpressing the human APP695sw mutation and the presenilin-1 mutation M146L (Tg PS1/APPsw) by immunostaining and ELISAs. An acute treatment with celastrol was investigated by administering celastrol intraperitoneally at a dosage of 1 mg/Kg in 35 week-old Tg PS1/APPsw for 4 consecutive days. In addition, a chronic treatment (32 days) with celastrol was tested using a matrix-driven delivery pellet system implanted subcutaneously in 5 month-old Tg PS1/APPsw to ensure a continuous daily release of 2.5 mg/Kg of celastrol.

Results

In vitro, celastrol dose dependently prevented NFκB activation and inhibited BACE-1 expression. Celastrol potently inhibited Aβ1-40 and Aβ1-42 production by reducing the β-cleavage of APP, leading to decreased levels of APP-CTFβ and APPsβ. In vivo, celastrol appeared to reduce the levels of both soluble and insoluble Aβ1-38, Aβ1-40 and Aβ1-42. In addition, a reduction in Aβ plaque burden and microglial activation was observed in the brains of Tg PS1/APPsw following a chronic administration of celastrol.

Conclusions

Overall our data suggest that celastrol is a potent Aβ lowering compound that acts as an indirect BACE-1 inhibitor possibly by regulating BACE-1 expression level via an NFκB dependent mechanism. Additional work is required to determine whether chronic administration of celastrol can be safely achieved with cognitive benefits in a transgenic mouse model of AD.

http://www.roskampinstitute.us/articles/archives/70

Has a Tobacco Company Stumbled on an Alzheimer’s Cure?

Nicotene-based compound at the heart of clinical studies

Mar 1, 2011, 10:33 am EDT   |   By Jeff Reeves, Editor, InvestorPlace.com

Tobacco stock Star Scientific (NASDAQ: CIGX) is a company that focuses on smokeless tobacco products. But if Star Scientific has its way, the public could have a very different perception of tobacco — namely, as the plant that cured Alzheimer’s. That could mean big things for tobacco, and even bigger things for Star Scientific stock.

http://www.investorplace.com/32191/star-scientific-tobacco-alzheimers-cure-treatment-anatabine-cigrx/

Roskamp Institute Obtains IRB Approval for Multi-Site Human Clinical Trial with Rock Creek Pharmaceutical RCP-006 Compound

on February 28, 2011

GLEN ALLEN, Va., Feb. 28, 2011 /PRNewswire via COMTEX/ –

http://www.starscientific.com/news/roskamp-institute-obtains-irb-approval-for-multi-site-human-clinical-trial-with-rock-creek-pharmaceutical-rcp-006-compound/

Role of Anatabine (RCP006 from Rock Creek Pharmaceuticals) as an anti-inflammatory agent

http://www.rfdn.org/inflammaging.html

Orally administrated cinnamon extract reduces β-amyloid oligomerization and corrects cognitive impairment in Alzheimer's disease animal models.

Frydman-Marom A, Levin A, Farfara D, Benromano T, Scherzer-Attali R, Peled S, Vassar R, Segal D, Gazit E, Frenkel D, Ovadia M.
Source

Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Tel Aviv, Israel.

PLoS One. 2011 Jan 28;6(1):e16564.

Abstract

An increasing body of evidence indicates that accumulation of soluble oligomeric assemblies of β-amyloid polypeptide (Aβ) play a key role in Alzheimer's disease (AD) pathology. Specifically, 56 kDa oligomeric species were shown to be correlated with impaired cognitive function in AD model mice. Several reports have documented the inhibition of Aβ plaque formation by compounds from natural sources. Yet, evidence for the ability of common edible elements to modulate Aβ oligomerization remains an unmet challenge. Here we identify a natural substance, based on cinnamon extract (CEppt), which markedly inhibits the formation of toxic Aβ oligomers and prevents the toxicity of Aβ on neuronal PC12 cells. When administered to an AD fly model, CEppt rectified their reduced longevity, fully recovered their locomotion defects and totally abolished tetrameric species of Aβ in their brain. Furthermore, oral administration of CEppt to an aggressive AD transgenic mice model led to marked decrease in 56 kDa Aβ oligomers, reduction of plaques and improvement in cognitive behavior. Our results present a novel prophylactic approach for inhibition of toxic oligomeric Aβ species formation in AD through the utilization of a compound that is currently in use in human diet.

PMID: 21305046 [PubMed] PMCID: PMC3030596
http://www.ncbi.nlm.nih.gov/pubmed/21305046
Full article: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0016564

Alzheimer's Risk Gene Disrupts Brain's Wiring 50 Years Before Disease Hits

ScienceDaily (May 16, 2011) — What if you were told you carried a gene that increases your risk for Alzheimer's disease? And what if you were told this gene starts to do its damage not when you're old but when you're young?...
http://www.sciencedaily.com/releases/2011/05/110513091638.htm

Naturally Occurring Plant Alkaloids Could Slow Down Alzheimer's Disease, Study Suggests

ScienceDaily (May 27, 2011) — A family of naturally occurring plant compounds could help prevent or delay memory loss associated with Alzheimer's disease, according to a new study by the Translational Genomics Research Institute (TGen).  Beta-carboline alkaloids could potentially be used in therapeutic drugs to stop, or at least slow down, the progressively debilitating effects of Alzheimer's, according to the study published recently in the scientific journal Public Library of Science (PLoS) One....
http://www.sciencedaily.com/releases/2011/05/110526131244.htm


Tobacco-Derived Compound Prevents Memory Loss in Alzheimer's Disease Mice

ScienceDaily (Apr. 28, 2011) — Cotinine, a compound derived from tobacco, reduced plaques associated with dementia and prevented memory loss in a mouse model of Alzheimer's disease, a study led by researchers at Bay Pines VA Healthcare System and the University of South Florida found... Some epidemiological studies showed that people who smoke tend to have lower incidences of Parkinson's disease and Alzheimer's disease. Studies have widely attributed this apparently beneficial effect to nicotine, which has been reported to improve memory and reduce Alzheimer's-like plaques in mice. However, nicotine's harmful cardiovascular effects and addictive properties make the compound a less than ideal drug candidate for neurodegenerative diseases.

The Bay Pines VA/USF team decided to look at the effects of cotinine, the major byproduct of nicotine metabolism, in Alzheimer's disease mice. Cotinine is nontoxic and longer lasting than nicotine. Furthermore, its safety has already been demonstrated in human trials evaluating cotinine's potential to relieve tobacco withdrawal symptoms...
http://www.sciencedaily.com/releases/2011/04/110427131824.htm

Here's the press release dated today 4-27-2011:

Tobacco-derived compound prevents memory loss in Alzheimer's disease mice

Tampa, FL (For immediate release) -- Cotinine, a compound derived from tobacco, reduced plaques associated with dementia and prevented memory loss in a mouse model of Alzheimer's disease, a study led by researchers at Bay Pines VA Healthcare System and the University of South Florida found.

The findings are reported online in the Journal of Alzheimer's Disease in advance of print publication...

More here: http://www.eurekalert.org/pub_releases/2011-04/uosf-tcp042711.php

Roskamp Institute to Begin Human Alzheimer's Clinical Trials With a Natural Compound in Tobacco
Oct 7, 2010

http://www.rfdn.org/news_release_100710.html

Also look into "Anatabloc" from Star Scientific.

DHA
http://alzheimers.infopop.cc/eve/forums/a/tpc/f/762104261/m/6894066487?r=8564020497#8564020497

Celiac disease
http://alzheimers.infopop.cc/eve/forums/a/tpc/f/762104261/m/9514085397

MRI May Predict Which Adults Will Develop Alzheimer's

ScienceDaily (Apr. 6, 2011) — Using MRI, researchers may be able to predict which adults with mild cognitive impairment are more likely to progress to Alzheimer's disease, according to the results of a study published online and in the June issue of Radiology...
http://www.sciencedaily.com/releases/2011/04/110406085054.htm

Compound Effectively Halts Progression of Multiple Sclerosis in Animal Model

ScienceDaily (Apr. 17, 2011) — Scientists from the Florida campus of The Scripps Research Institute have developed the first of a new class of highly selective compounds that effectively suppresses the severity of multiple sclerosis in animal models. The new compound could provide new and potentially more effective therapeutic approaches to multiple sclerosis and other autoimmune diseases that affect patients worldwide...
http://www.sciencedaily.com/releases/2011/04/110418093846.htm

Progression of Smell Loss Offers Clues to the Treatment of Alzheimer's Disease

ScienceDaily (Apr. 6, 2011) — Loss of smell is a characteristic early symptom among people with Alzheimer's disease, but the relationship between olfactory dysfunction and the progression of the disease is still relatively unknown... Removing one olfactory bulb lowered the amount of Aβ found 6 months later on that side of the brain by more than 50 percent, even in regions that receive no direct olfactory bulb input. This supports a role for early-life olfactory bulb output in the spread of Aβ throughout the brain...
http://www.sciencedaily.com/releases/2011/04/110406192513.htm



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Updated: August 27, 2011
Inception: August 27, 2011