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- Tetracycline -


General Information:

Names:
Wikipedia entry:
Dr. Ray Shahelien entry: 

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Observations:

Tetracycline - Disassemble amyloid beta, suppress or eliminate spirochete
            of the brain.
[ Need link to source of the above about amyloid beta... in Neurospirochetosis page?]

Tetracyclines (Tetracycline, Doxycycline)

Could low-dosage of Doxycycline be considered for Alzheimer's disease treatment?
S.A. KAMER, and A.R. KAMER, New York University, New York, NY
July 2010


Objectives: Alzheimer's disease (AD) is a neurodegenerative disease primarily of the elderly, and treatment modalities are limited. AD is characterized by the presence of senile plaques with its main component amyloid , neurofibrillary tangles with phosphophorylated tau protein, and neuronal loss. These pathological components as well as inflammation are hypothesized to be involved in the pathogenesis of AD.

When considering potential treatment modalities for AD, this pathogenesis should be considered. Periostat is a drug containing low dosages of Doxycycline and is used in long-term administration to treat periodontal disease without the side effects characterizing the anti-microbial doses of this medication.

The objective of this study is to evaluate the possible use of Periostat for treating AD by critically analyzing the existing literature.

Methods: a Medline search was undertaken using combinations of the following terms: doxycycline, tetracycline, minocycline, Alzheimer's disease, cognition, mild impairment cognition, metalloproteinase (MMP), amyloid, and inflammation. Then, the relevant papers were reviewed manually.

Results: the database search resulted in a total 301 papers containing the search terms. Further evaluation resulted in 45 papers containing relevant data. The studies evaluated were based on in vitro, animal, and clinical data.

Only one randomized control study was found. The review study found that tetracycline derivatives, including doxycycline:

cross the brain blood barrier;
b) have neuroprotective effects;
c) destabilize the amyloid fibrils to make them susceptible to proteolysis;
d) inhibit caspase-3 that has a role in tau protein neurotoxicity;
e) inhibit the production of proinflammatory molecules; and
f) slow cognitive decline.

However, untoward effects have also been reported related to tetracyclines anti-MMPs activities.

Conclusion: the available data suggest that in selective cases low dosage doxycycline may be effective in treating AD.
http://iadr.confex.com/iadr/2010barce/preliminaryprogram/abstract_140673.htm


A randomized, controlled trial of doxycycline and rifampin for patients with Alzheimer's disease.
J Am Geriatr Soc. 2004 Mar;52(3):381-7.

Abstract

OBJECTIVES: To assess whether doxycycline and rifampin have a therapeutic role in patients with Alzheimer's disease (AD).

DESIGN: Randomized, triple-blind, controlled trial.

SETTING: Three tertiary care and two community geriatric clinics in Canada.

PARTICIPANTS: One hundred one patients with probable AD and mild to moderate dementia.

INTERVENTION: Oral daily doses of doxycycline 200 mg and rifampin 300 mg for 3 months.

MEASUREMENTS:

The primary outcome was a change in Standardized Alzheimer's Disease Assessment Scale cognitive subscale (SADAScog) at 6 months. Secondary outcomes were changes in the SADAScog at 12 months and tests of dysfunctional behavior, depression, and functional status.

RESULTS:
There was significantly less decline in the SADAScog score at 6 months in the antibiotic group than in the placebo group, (-2.75 points, 95% confidence interval (CI)=-5.28 to -0.22, P=.034). At 12 months, the difference between groups in the SADAScog was -4.31 points (95% CI=-9.17-0.56, P=.079). The antibiotic group showed significantly less dysfunctional behavior at 3 months. There was no significant difference in adverse events between groups (P=.34). There were no differences in Chlamydia pneumoniae detection using polymerase chain reaction or antibodies (immunoglobulin (Ig)G or IgA) between groups.

CONCLUSION: Therapy with doxycycline and rifampin may have a therapeutic role in patients with mild to moderate AD. The mechanism is unlikely to be due to their effect on C. pneumoniae. More research is needed to investigate these agents.

http://www.ncbi.nlm.nih.gov/pubmed/14962152


Anti-amyloidogenic activity of tetracyclines: studies in vitro.
Forloni G, Colombo L, Girola L, Tagliavini F, Salmona M.
Source: Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. forloni@irfmn.mnegri.it
FEBS Lett. 2001 Jan 5;487(3):404-7.

Abstract

Cerebral deposition of beta-amyloid is a major neuropathological feature in Alzheimer's disease. Here we show that tetracyclines, tetracycline and doxycycline, classical antibiotics, exhibit anti-amyloidogenic activity. This capacity was determined by the exposure of beta 1-42 amyloid peptide to the drugs followed by the electron microscopy examination of the amyloid fibrils spontaneously formed and quantified with thioflavine T binding assay. The drugs reduced also the resistance of beta 1-42 amyloid fibrils to trypsin digestion. Tetracyclines not only inhibited the beta-amyloid aggregates formation but also disassembled the pre-formed fibrils. The results indicate that drugs with a well-known clinical profile, including activity in the central nervous system, are potentially useful for Alzheimer's therapy.
PMID: 11163366 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/11163366

My thought is, if as a teenager, my dermatologist can have me taking low dose tetracycline for 4 years to fight acne, why can't someone with dementia try it?

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Updated: July 2, 2012
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