X-Message-Number: 32233
Date: Thu, 17 Dec 2009 21:15:14 -0800 (PST)
Subject: evidence based OTC treatment of Alzheimer's disease I

[Clinical trials with over-the-counter supplements have concentrated either on 
items which suppress inflammation, or on antioxidants which scavenge oxygen 
derived free radicals. Most of these items have proved to be worthless in the 
treatment of Alzheimer's disease. Similarly most drugs used to treat Alzheimer's
disease do little to slow the deterioration, but instead offer a mild temporary
symptom relief. However, evidence has been accumulating that the primary driver
of Alzheimer's disease is a nitrogen derived free radical called peroxynitrite,
which may mediate both amyloid and tau accumulation as well as their toxicity. 
Excellent results have been obtained with peroxynitrite scavengers, with 
reversals of Alzheimer's disease in human clinical trials being repeatedly 
demonstrated. IMHO, the only thing which may be  preventing the abolition of 
Alzheimer's disease is the mental inertia of scientists, as well as the 
bureaucrats who fund them. Unfortunately, most bureaucrats keep throwing money 
into repeatedly testing discredited interventions, while ignoring successful 
ones. Common sense is anything but...]

[Abolition of amyloid induced memory deficits by rosmarinic acid is due to 
peroxynitrite scavenging.]

Behav Brain Res. 2007 Jun 18;180(2):139-45. Epub 2007 Mar 12.

A natural scavenger of peroxynitrites, rosmarinic acid, protects against 
impairment of memory induced by Abeta(25-35).

Alkam T, Nitta A, Mizoguchi H, Itoh A, Nabeshima T. Department of 
Neuropsychopharmacology & Hospital Pharmacy, Nagoya University Graduate School 
of Medicine, Nagoya 466-8560, Japan.

    Peroxynitrite (ONOO(-))-mediated damage is regarded to be responsible for 
    the cognitive dysfunction induced by amyloid beta protein (Abeta) in 
    Alzheimer's disease (AD). In the present study, we examined the protective 
    effects of rosmarinic acid (RA), a natural scavenger of ONOO(-), on the 
    memory impairment in a mouse model induced by acute i.c.v. injection of 
    Abeta(25-35). Mice daily received i.p. several doses of RA after the 
    injection of Abeta(25-35). RA prevented the memory impairments induced by 
    Abeta(25-35) in the Y maze test and novel object recognition task. RA, at 
    the effective lowest dose (0.25mg/kg), prevented Abeta(25-35)-induced 
    nitration of proteins, an indirect indicator of ONOO(-) damage, in the 
    hippocampus. At this dose, RA also prevented nitration of proteins and 
    impairment of recognition memory induced by ONOO(-)-i.c.v.-injection. 
    Co-injection of the non-memory-impairing dose of ONOO(-) with Abeta(25-35) 
    blocked the protective effects of RA (0.25mg/kg). These results demonstrated
    that the memory protective effects of RA in the neurotoxicity of 
    Abeta(25-35) is due to its scavenging of ONOO(-), and that daily consumption
    of RA may protect against memory impairments observed in AD.
PMID: 17420060

[Peroxynitrite is linked to the accumulation of tau filaments.]

Am J Pathol. 2003 Sep;163(3):1021-31.
Nitration of tau protein is linked to neurodegeneration in tauopathies.

Horiguchi T, Uryu K, Giasson BI, Ischiropoulos H, LightFoot R, Bellmann C, 
Richter-Landsberg C, Lee VM, Trojanowski JQ. Department of Pathology and 
Laboratory Medicine, Center for Neurodegenerative Disease Research, Institute on
Aging, University of Pennsylvania School of Medicine, Philadelphia, PA 
19104-4283, USA.
Erratum in:  Am J Pathol. 2003 Dec;163(6):2645.

    Oxidative and nitrative injury is implicated in the pathogenesis of 
    Alzheimer's disease (AD) and Down syndrome (DS), but no direct evidence 
    links this type of injury to the formation of neurofibrillary tau lesions. 
    To address this, we generated a monoclonal antibody (mAb), n847, which 
    recognizes nitrated tau and alpha-synuclein. n847 detected nitrated tau in 
    the insoluble fraction of AD, corticobasal degeneration (CBD), and Pick's 
    disease (PiD) brains by Western blots. Immunohistochemistry (IHC) showed 
    that n847 labeled neurons in the hippocampus and neocortex of AD and DS 
    brains. Double-label immunofluorescence with n847 and an anti-tau antibody 
    revealed partial co-localization of tau and n847 positive tangles, while 
    n847 immunofluorescence and Thioflavin-S double-staining showed that a 
    subset of n847-labeled neurons were Thioflavin-S-positive. In addition, 
    immuno-electron microscopy revealed that tau-positive filaments in 
    tangle-bearing neurons were also labeled by n847 and IHC of other 
    tauopathies showed that some of glial and neuronal tau pathologies in CBD, 
    progressive supranuclear palsy, PiD, and frontotemporal dementia with 
    parkinsonism linked to chromosome 17 also were n847-positive. Finally, 
    nitrated and Thioflavin-S-positive tau aggregates were generated in a 
    oligodendrocytic cell line after treatment with peroxynitrite. Taken 
    together, these findings imply that nitrative injury is directly linked to 
    the formation of filamentous tau inclusions.
PMID: 12937143
Free text>

Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=32233

Warning: This message was filtered from the daily CryoNet digest
because the poster sent too many messages per digest.
It thus may need to be rated.