1229 replies to this topic

[tham]

" Remember this: Before the age of processed foods (from the
1950's on), Alzheimer's was an extremely rare condition. It
was so rare that doctors traveled long distances just to study
the brains of people who died with the condition. A century ago,
Alzheimer's disease was an oddity; today it's the norm. And
our processed food diets are largely to blame. "


http://www.naturalne...anti-aging.html

[tham]

Sage and Alzheimer's.


http://www.nutraingr...for-Alzheimer-s

http://jpet.aspetjou...317/3/1143.full


http://www.medicinal...e-benefits.html

http://www.mamaherb....medy-using-sage

http://seniors-healt...heimers-disease

http://www.ncbi.nlm....t_uids=12895683



Salvia miltiorrhiza, Chinese sage.

http://en.wikipedia....ia_miltiorrhiza

http://www.ncbi.nlm....t_uids=19154776

http://www.ncbi.nlm....t_uids=17504224

[Nigel Kinbrum]

I've only just noticed this thread. I've written a few blog posts covering the subject:-

Vitamin D
Look after your brain.
Look after your brain, Part 2.
Look after your brain, Part 3.
Look after your brain, Part 4.
Dementia: A review of the evidence.

Unfortunately, when someone becomes institutionalised due to dementia, we lose control over their diet & supplement regime. I'm hoping to see a dietician so that I can re-introduce the above supplements after I was ordered to withdraw them by the nursing home.

Edited by Nigeepoo, 29 March 2010 - 03:22 PM.

[tham]

" Given the side effect profile of prescribed cholinesterase inhibitors,
and a current lack of a well tolerated nicotinic receptor agonist, these
herbal treatments may well provide effective and well-tolerated
treatments for dementia, either alone, in combination, or as an
adjunct to conventional treatments. "

http://www.benthamdi...00035/0008B.SGM

[tham]

Spanish Sage, lemon balm, aromatherapy.


http://www.aromamd.n...rs_dementia.pdf

http://www.life-enha...late.asp?ID=947

http://www.life-enha...late.asp?ID=906

http://alzheimers.or...mp;pageNumber=2

[Mind]

" Remember this: Before the age of processed foods (from the
1950's on), Alzheimer's was an extremely rare condition. It
was so rare that doctors traveled long distances just to study
the brains of people who died with the condition. A century ago,
Alzheimer's disease was an oddity; today it's the norm. And
our processed food diets are largely to blame. "


http://www.naturalne...anti-aging.html

Remember that there are likely some confounding variables in this anecdotal evidence. Lifespans have increased, making it more likely that people will live to the age where they will get Alzheimer's and other degenerative brain diseases. Also, people have become more sedentary and obese.

No doubt a good diet and lifestyle is beneficial, but I wouldn't say it is a 100% guaranteed way to ward off Alzheimer's

[Fleet]

[tham]

Unfortunately, when someone becomes institutionalised due to dementia,
we lose control over their diet & supplement regime. I'm hoping to see
a dietician so that I can re-introduce the above supplements after I was
ordered to withdraw them by the nursing home.

This is very true.

I have no control whatsoever over my father's supplement
regimen - in fact, he's taking none now.

http://www.imminst.o...o...st&p=381720


My elder brother, a totally non-life extensionist, is the main
obstacle. Standing outside his gate one night as usual, arguing
with him over the value of supplements/herbs/homeopathy in
treating, or al least slowing down my father's condition, he
reasoned back - if I couldn't handle my own eczema, IBS, etc.,
what did I think I could do for a far more difficult disease - dementia ?
(i.e. tantamount to a not-very-good-looking beautician trying
to convince him to buy a bottle of beauty cream !) .

Months ago, I tried to give him a bottle of Jarrow's CarnitAll to
him to pass to my father's nursing home's Sri Lankan caretaker
guy (over whom he instructs his drug regimen). It's now lying
redundant on my office table. I just started taking one today.

Links to CDP choline, lemon balm, etc sent to his email
(and my sister's too) went unnoticed. I won't be bothering to
send links to alpha GPC or Spanish sage as well.

He's never heard of ALCAR, and trying to explain it to him,
he thought it's similar to L-carnitine, common in pharmacies
here.

Neither has he heard of phosphatidylserine. And limited as
the range of supplements are in Malaysia, Stay-Well's
"Memosential" - which has ALCAR with PS, which may very
well have prevented my father's post-stroke condition from
deteriorating into dementia in the first place - has been around
in the local pharmacies (very few health food stores here) for years.


http://www.mariniaga...l.aspx?key=2958

[tunt01]

http://www.scienceda...00401173730.htm

Drug That Extends Life Span Prevents Alzheimer's Deficits

[tham]

Review of herbs for Alzheimer's, including ginkgo, huperzine A and ginseng.

http://ecam.oxfordjo...p;pmid=19737808

[tunt01]

Spanish Sage, lemon balm, aromatherapy.


http://www.aromamd.n...rs_dementia.pdf

this was interesting. thanks for posting it. my confidence in sage/rosmarinic acid delaying/halting the progression of alzheimer's continues to build.

[NDM]

Spanish Sage, lemon balm, aromatherapy.


http://www.aromamd.n...rs_dementia.pdf

this was interesting. thanks for posting it. my confidence in sage/rosmarinic acid delaying/halting the progression of alzheimer's continues to build.

I wonder...The thing is both sage and rosemary also have anti-hsv activity...and the herpes virus has been linked with alzheimer...so part of the mechanism of action might turn out to be via anti-hsv activity.

[AgeVivo]

http://www.scienceda...00401173730.htm

Drug That Extends Life Span Prevents Alzheimer's Deficits

rapamycin again and again; nice

[tham]

Aibo, the elderly and dementia.

http://www.interacti...ves-of-elderly/


http://www.ncbi.nlm....t_uids=18294600

http://www.ncbi.nlm....t_uids=18002332

http://www.ncbi.nlm....t_uids=14718491

http://www.ncbi.nlm....t_uids=11974948


!'ve been thinking of getting Aibo for my father for
some time, the main prohibitive factor being its cost,
and the only ones on the market are secondhand -
Sony stopped making it a long time ago.

The second choice is the Korean Genibo, at about half
the cost, but its motions seem to be less lifelike.
The upside is one can buy it new.

http://www.robotoys....html?p_catid=98


The third choice is I-Cybie, a Hongkong product, fairly
cheap at about $200, a tenth that of Aibo. Out of production
too, and the ones on Ebay appear to be the first batch which
had problems with a critical servo motor. Not very intelligent,
but one can't expect much for its price. Its developers said
that Aibo had far better servos.

[tham]

The links on Aibo and the following has been posted on
the "Avatar" thread under the "Introduction" subforum,
but I consider it so important that I'll post it here as well.

Human beings have always been, and will always be,
socially interactive creatures. I believe this is the single
most important overriding factor governing life expectancy,
notwithstanding any diet, lifestyle, supplement regimen
or other life extension technique one may practise.

I'm stll trying to find the link to it, but there was a report
about a tiny community of exceptionally long-lived inhabitants
in a small village, I think Peruvian or Mexican, some years ago.
When scientists went there to study their lifestyles to find out
the clues to their longevity, they found that their houses were
arranged in a small circle, with the furthest neighbour, i.e.
the one directly opposite, just feet away.

Every evening, each neighbour took out their chairs to the
center of the small compound, sitting around to enjoy some
good conversation.

Take away this most fundamental human need, and the best
supplements in the world will come to nothing.


I read this in Time Magazine over 30 years ago, and still
remember it very well.


http://www.time.com/...,915397,00.html

A similar result is found among human patients — even
people in deep comas often show improved heart rates
when their hands are held by doctors or nurses, Lynch's
point is that medical personnel intuitively know the
healing value of the human touch but sometimes manage
to overlook the principle because it seems unscientific.

The above is very true. I've had first hand experience of this.
13 years ago, my mother suffered a massive hemorrhagic
stroke and went into a deep coma. As they were wheeling
her to the operating theater, I accompanied her trolley.

On the way there, I called out her name and held her hand
several times. I was stunned and puzzled, when, each time
I did so, her blood pressure and heart rate, which had both
been relatively high, dropped INSTANTLY, as could be seen
from the digital monitor. The moment I let go my hand, both
shot up again spontaneously.

[Sillewater]

Omega-3 fatty acids: potential role in the management of early Alzheimer’s disease

Has some interesting discussion about AD, O-3, and ApoE

[tham]

This confirms the benefits of Aibo.

http://www.newswise....es/view/517077/


" ..... hypertensive New York stockbrokers who got dogs
or cats were found to have lower blood pressure and heart
rates than those who didn’t get pets. "

http://stress.about....tsandstress.htm


Animal-assisted therapy and dementia.

http://www.ncbi.nlm....t_uids=16640796

http://www.animaltherapy.net/

http://www.therapet.com/

[tham]

James Lynch, author of the book in the
Time Magazine writeup above.

http://www.takingcha...w-james-lynch-0


John Cacioppo and Louise Hawkley, two further
investigators of loneliness.

http://www-news.uchi...oneliness.shtml

http://www.psychosom...t/full/64/3/407

http://www.allvoices...ed-news/5455615


Loneliness and CHD in women.

http://www.ncbi.nlm....t_uids=19661189


Loneliness and breast cancer.

http://www.ajc.com/h...brs/631464.html

http://www.ncbi.nlm....t_uids=15863708


" Most positive evidence has been accumulated from studies
on the influence of loneliness on cardiovascular morbidity and mortality. Animal experiments have demonstrated repeatedly
that psychological stress evoked by aversive sensoric stimuli
or unsuccessful social striving induce cardiovascular pathology including myocardial damage, hypertension, vascular changes and increased risk of sudden cardiac death. "

http://www.ncbi.nlm....st_uids=2889418


" Among the 38 statements in NHP as a judgment of quality
of life prior to CABG, one of them, "I feel lonely" was
independently associated with survival both at 30 days
and 5 years after CABG. "

http://www.ncbi.nlm....st_uids=9728430



http://www.sciencebl...r_heart_disease

http://www.ncbi.nlm....t_uids=12434940

http://www.ncbi.nlm....t_uids=19413133

Edited by tham, 17 April 2010 - 07:37 PM.

[Sillewater]

Exp Neurol. 2009 Aug;218(2):286-92. Epub 2009 Apr 7.
Amyloid beta, mitochondrial structural and functional dynamics in Alzheimer's disease.
Reddy PH.

Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, 97006, USA. reddyh@ohsu.edu
Abstract
Mitochondria are the major source of energy for the normal functioning of brain cells. Increasing evidence suggests that the amyloid precursor protein (APP) and amyloid beta (Abeta) accumulate in mitochondrial membranes, cause mitochondrial structural and functional damage, and prevent neurons from functioning normally. Oligomeric Abeta is reported to induce intracellular Ca(2+) levels and to promote the excess accumulation of intracellular Ca(2+) into mitochondria, to induce the mitochondrial permeability transition pore to open, and to damage mitochondrial structure. Based on recent gene expression studies of APP transgenic mice and AD postmortem brains, and APP/Abeta and mitochondrial structural studies, we propose that the overexpression of APP and the increased production of Abeta may cause structural changes of mitochondria, including an increase in the production of defective mitochondria, a decrease in mitochondrial trafficking, and the alteration of mitochondrial dynamics in neurons affected by AD. This article discusses some critical issues of APP/Abeta associated with mitochondria, mitochondrial structural and functional damage, and abnormal intracellular calcium regulation in neurons from AD patients. This article also discusses the link between Abeta and impaired mitochondrial dynamics in AD.

PMID: 19358844 [PubMed - indexed for MEDLINE]PMCID: PMC2710427 [Available on 2010/8/1]

J Bioenerg Biomembr. 2009 Oct;41(5):441-6.
Oxidatively modified, mitochondria-relevant brain proteins in subjects with Alzheimer disease and mild cognitive impairment.
Sultana R, Butterfield DA.

Department of Chemistry, University of Kentucky, Lexington, KY 40506-0055, USA.
Abstract
Alzheimer disease (AD) is an age-related neurodegenerative disorder, characterized histopathologically by the presence of senile plaques (SP), neurofibrillary tangles and synapse loss in selected brain regions. Positron emission tomography (PET) studies of glucose metabolism revealed decreased energetics in brain of subjects with AD and arguably its earliest form, mild cognitive impairment (MCI), and this decrease correlated with brain structural studies using MRI. The main component of senile plaques is amyloid beta-peptide (Abeta), a 40-42 amino acid peptide that as oligomers is capable of inducing oxidative stress under both in vitro and in vivo conditions and is neurotoxic. In the mitochondria isolated from AD brain, Abeta oligomers that correlated with the reported increased oxidative stress markers in AD have been reported. The markers of oxidative stress have been localized in the brain regions of AD and MCI that show pathological hallmarks of this disease, suggesting the possible role of Abeta in the initiation of the free-radical mediated process and consequently to the build up oxidative stress and AD pathogenesis. Using redox proteomics our laboratory found a number of oxidatively modified brain proteins that are directly in or are associated with the mitochondrial proteome, consistent with a possible involvement of the mitochondrial targeted oxidatively modified proteins in AD progression or pathogenesis. The precise mechanistic link between mitochondrial oxidative damage and role of oligomeric Abeta has not been explicated. In this review, we discuss the role of the oxidation of mitochondria-relevant brain proteins to the pathogenesis and progression of AD.

PMID: 19777328 [PubMed - indexed for MEDLINE]

Drugs Aging. 2010 Mar 1;27(3):181-92. doi: 10.2165/11532140-000000000-00000.
Mitochondrial dynamics in Alzheimer's disease: opportunities for future treatment strategies.
Bonda DJ, Wang X, Perry G, Smith MA, Zhu X.

Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Abstract
The complexities that underlie the cognitive impairment and neurodegeneration characteristic of Alzheimer's disease (AD) have yet to be completely understood, although many factors in disease pathogenesis have been identified. Particularly important in disease development seem to be mitochondrial disturbances. As pivotal role players in cellular metabolism, mitochondria are pertinent to cell survival and thus any deviation from their operation is certainly fatal. In this review, we describe how the dynamic balance of mitochondrial fission and fusion in particular is a necessary aspect of cell proliferation and that, as the cell ages, such balance is inevitably compromised to yield a destructive environment in which the cell cannot exist. Evidence for such disturbance is abundant in AD. Specifically, the dynamic balance of fission and fusion in AD is greatly shifted toward fission, and, as a result, affected neurons contain abnormal mitochondria that are unable to meet the metabolic demands of the cell. Moreover, mitochondrial distribution in AD cells is perinuclear, with few metabolic organelles in the distal processes, where they are normally distributed in healthy cells and are needed for exocytosis, ion channel pumps, synaptic function and other activities. AD neurons are thus characterized by increases in reactive oxidative species and decreases in metabolic capability, and, notably, these changes are evident very early in AD progression. We therefore believe that oxidative stress and altered mitochondrial dynamics contribute to the precipitation of AD pathology and thus cognitive decline. These implications provide a window for therapeutic intervention (i.e. mitochondrial protection) that has the potential to significantly deter AD progression if adequately developed. Current treatment strategies under investigation are described in this review.

PMID: 20210366 [PubMed - in process]

Curr Alzheimer Res. 2008 Oct;5(5):457-68.
Mitochondria, mitochondrial DNA and Alzheimer's disease. What comes first?
Mancuso M, Orsucci D, Siciliano G, Murri L.

Department of Neuroscience, Neurological Clinic, University of Pisa, Italy. mmancuso@inwind.it
Abstract
To date, the beta amyloid (Abeta) cascade hypothesis remains the main pathogenetic model of Alzheimer's disease (AD), but its role in the majority of sporadic AD cases is unclear. The mitochondria play central role in the bioenergetics of the cell and apoptotic cell death. In the past 20 years research has been directed at clarifying the involvement of mitochondria and defects in mitochondrial oxidative phosphorylation in late-onset neurodegenerative disorders, including AD. Morphological, biochemical and genetic abnormalities of the mitochondria in several AD tissues have been reported. Impaired mitochondrial respiration, particularly COX deficiency, has been observed in brain, platelets and fibroblasts of AD patients. The "mitochondrial cascade hypothesis" could explain many of the biochemical, genetic and pathological features of sporadic AD. Somatic mutations in mitochondrial DNA (mtDNA) could cause energy failure, increased oxidative stress and accumulation of Abeta, which in a vicious cycle reinforces the mtDNA damage and the oxidative stress. Despite the evidence of mitochondrial dysfunction in AD, no causative mutations in the mtDNA have been detected so far. Indeed, results of studies on the role of mtDNA haplogroups in AD are controversial. In this review we discuss the role of the mitochondria in the cascade of events leading to AD, and we will try to provide an answer to the question "what comes first".

PMID: 18855587 [PubMed - indexed for MEDLINE]

EMBO J. 2008 Jan 23;27(2):306-14.
Quality control of mitochondria: protection against neurodegeneration and ageing.
Tatsuta T, Langer T.

Institute for Genetics and Centre for Molecular Medicine, University of Cologne, Cologne, Germany.
Abstract
Dysfunction of mitochondria has severe cellular consequences and is linked to ageing and neurodegeneration in human. Several surveillance strategies have evolved that limit mitochondrial damage and ensure cellular integrity. Intraorganellar proteases conduct protein quality control and exert regulatory functions, membrane fusion and fission allow mitochondrial content mixing within a cell, and the autophagic degradation of severely damaged mitochondria protects against apoptosis. Here, we will summarize the current knowledge on these surveillance strategies and their role in human disease.

PMID: 18216873 [PubMed - indexed for MEDLINE]PMCID: PMC2234350

Biochim Biophys Acta. 2008 Jul-Aug;1777(7-8):794-9. Epub 2008 Mar 29.
Oxidative stress and mitochondrial dysfunction in neurodegeneration; cardiolipin a critical target?
Pope S, Land JM, Heales SJ.

Neurometabolic Unit, National Hospital, UCLH Foundation Trust, UCL, Queen Square, London, WC1N 3BG, UK.
Abstract
Oxidative stress and subsequent impairment of mitochondrial function is implicated in the neurodegenerative process and hence in diseases such as Parkinson's and Alzheimer's disease. Within the brain, neuronal and astroglial cells can display a differential susceptibility to oxidant exposure. Thus, astrocytes can up regulate glutathione availability and, in response to mitochondrial damage, glycolytic flux. Whilst neuronal cells do not appear to possess such mechanisms, neuronal glutathione status may be enhanced due to the trafficking of glutathione precursors from the astrocyte. However, when antioxidants reserves are not sufficient or the degree of oxidative stress is particularly great, mitochondrial damage occurs, particularly at the level of complex IV (cytochrome oxidase). Whilst the exact mechanism for the loss of activity of this enzyme complex is not know, it is possible that loss and/or oxidative modification of the phospholipid, cardiolipin is a critical factor. Consequently, in this short article, we also consider (a) cardiolipin metabolism and function, (b) the susceptibility of this molecule to undergo oxidative modification following exposure to oxidants such as peroxynitrite, © loss of mitochondrial cardiolipin in neurodegenerative disorders, (d) methods of detecting cardiolipin and (e) possible therapeutic strategies that may protect cardiolipin from oxidative degradation.

PMID: 18420023 [PubMed - indexed for MEDLINE]

Maybe melatonin would help:

Rejuvenation Res. 2008 Oct;11(5):935-43.
Melatonin prevents age-related mitochondrial dysfunction in rat brain via cardiolipin protection.
Petrosillo G, Fattoretti P, Matera M, Ruggiero FM, Bertoni-Freddari C, Paradies G.

Department of Biochemistry and Molecular Biology, CNR Institute of Biomembranes and Bioenergetics, University of Bari, Bari Italy.
Abstract
Reactive oxygen species (ROS) are considered a key factor in brain aging process. Complex I of the mitochondrial respiration chain is an important site of ROS production and hence a potential contributor to brain functional changes with aging. Appropriate antioxidant strategies could be particularly useful to limit this ROS production and associated mitochondrial dysfunction. Melatonin has been shown to possess antioxidant properties and to reduce oxidant events in brain aging. The mechanism underlying this protective effect of melatonin is not well established. In the present study, we examined the effects of long-term treatment of aged rats with melatonin on various parameters related to mitochondrial bioenergetics in brain tissue. After isolation of mitochondria from control, aged, and melatonin-treated young and aged rats, various bioenergetic parameters were evaluated such as complex I activity, rates of state 3 respiration, mitochondrial hydrogen peroxide (H2O2) production, and membrane potential. The mitochondrial content of normal and oxidized cardiolipin was also evaluated. We found that all these mitochondrial parameters were significantly altered with aging, and that melatonin treatment completely prevented these age-related alterations. These effects appear to be due, at least in part, to melatonin's ability to preserve the content and structural integrity of cardiolipin molecules, which play a pivotal role in mitochondrial bioenergetics. The melatonin's ability to prevent complex I dysfunction and cardiolipin peroxidation was also demonstrated by in vitro experiments on brain mitochondria treated with tert-butyl hydroperoxide. In summary, this study documents a decline of mitochondrial bioenergetic functions in brain with aging and the beneficial effect of melatonin.

PMID: 18928424 [PubMed - indexed for MEDLINE]

or Estrogen:

Mol Cell Endocrinol. 2008 Aug 13;290(1-2):51-9. Epub 2008 May 2.
Estrogen actions on mitochondria--physiological and pathological implications.
Simpkins JW, Yang SH, Sarkar SN, Pearce V.

Department of Pharmacology & Neuroscience, Institute for Aging and Alzheimer's Disease Research, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA. Jsimpkin@hsc.unt.edu
Abstract
Estrogens are potent neuroprotective hormones and mitochondria are the site of cellular life-death decisions. As such, it is not surprising that we and others have shown that estrogens have remarkable effects on mitochondrial function. Herein we provide evidence for a primary effect of estrogens on mitochondrial function, achieved in part by the import of estrogen receptor beta (ERbeta) into the mitochondria where it mediates a number of estrogen actions on this vital organelle. ERbeta is imported into the mitochondria, through tethering to cytosolic chaperone protein and/or through direct interaction with mitochondrial import proteins. In the mitochondria, ERbeta can affect transcription of critical mitochondrial genes through the interaction with estrogen response elements (ERE) or through protein-protein interactions with mitochondrially imported transcription factors. The potent effects of estrogens on mitochondrial function, particularly during mitochondrial stress, argues for a role of estrogens in the treatment of mitochondrial defects in chronic neurodegenerative diseases like Alzheimer's disease (AD) and Parkinson's disease (PD) and more acute conditions of mitochondrial compromise, like cerebral ischemia and traumatic brain injury.

PMID: 18571833 [PubMed - indexed for MEDLINE]PMCID: PMC2737506

Alpha Lipoic Acid, ALCAR, CoQ10. I recall a protocol out there that uses these for AD:

Neurochem Res. 2008 Jan;33(1):194-203. Epub 2007 Jun 29.
The effects and mechanisms of mitochondrial nutrient alpha-lipoic acid on improving age-associated mitochondrial and cognitive dysfunction: an overview.
Liu J.

Institute for Brain Aging and Dementia, University of California, 1261 Gillespie Neuroscience Research Facility, Irvine, CA 92697, USA. j.liu@uci.edu
Abstract
We have identified a group of nutrients that can directly or indirectly protect mitochondria from oxidative damage and improve mitochondrial function and named them "mitochondrial nutrients". The direct protection includes preventing the generation of oxidants, scavenging free radicals or inhibiting oxidant reactivity, and elevating cofactors of defective mitochondrial enzymes with increased Michaelis-Menten constant to stimulate enzyme activity, and also protect enzymes from further oxidation, and the indirect protection includes repairing oxidative damage by enhancing antioxidant defense systems either through activation of phase 2 enzymes or through increase in mitochondrial biogenesis. In this review, we take alpha-lipoic acid (LA) as an example of mitochondrial nutrients by summarizing the protective effects and possible mechanisms of LA and its derivatives on age-associated cognitive and mitochondrial dysfunction of the brain. LA and its derivatives improve the age-associated decline of memory, improve mitochondrial structure and function, inhibit the age-associated increase of oxidative damage, elevate the levels of antioxidants, and restore the activity of key enzymes. In addition, co-administration of LA with other mitochondrial nutrients, such as acetyl-L: -carnitine and coenzyme Q10, appears more effective in improving cognitive dysfunction and reducing oxidative mitochondrial dysfunction. Therefore, administrating mitochondrial nutrients, such as LA and its derivatives in combination with other mitochondrial nutrients to aged people and patients suffering from neurodegenerative diseases, may be an effective strategy for improving mitochondrial and cognitive dysfunction.

PMID: 17605107 [PubMed - indexed for MEDLINE]

ECGC also helps:

Int J Dev Neurosci. 2009 May;27(3):223-31. Epub 2009 Jan 20.
Mitochondrial alterations in aging rat brain: effective role of (-)-epigallo catechin gallate.
Srividhya R, Zarkovic K, Stroser M, Waeg G, Zarkovic N, Kalaiselvi P.

Department of Medical Biochemistry, Dr. A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, India.
Abstract
Aging is a multi-factorial process which involves deprivation in body's metabolism. Brain mitochondria are prone to oxidative damage owing to their high metabolic rate. The decline in antioxidant system during aging augments the neuronal damage to mitochondrial components like antioxidant system, Kreb's cycle enzymes and electron transport chain complexes. Since brain is an organ rich in fatty acids, lipid peroxidation products like hydroxynonenal are predominant. Those lipid peroxidation products conjugate with amino acids to form adducts which alter their structural and functional properties. Epigallo catechin gallate is a potent antioxidant which is rich in green tea extract. This study elucidated the antioxidant potential of epigallo catechin gallate to counteract the mitochondrial oxidative damage in brain. The study comprised of young (3-4 months old; 150+/-20 g) and aged (above 24 months; 420+/-20 g) male albino rats of Wistar strain in Groups I and II. Groups III and IV comprised of young and aged rats supplemented with epigallo catechin gallate (2mg/kg body weight) for 30 days. Antioxidants, Kreb's cycle enzymes and electron transport chain complexes were assayed in the mitochondrial fraction. Hydroxynonenal expression was carried out using immunohistochemical analysis. Epigallo catechin gallate supplementation decreased the expression of hydroxynonenal in aged brain, up-regulated the antioxidant system and augmented the activities of Kreb's cycle enzymes and electron transport chain complexes in aged brain mitochondria thus proving its antioxidant potential at the level of mitochondria.

PMID: 19429387 [PubMed - indexed for MEDLINE]

[Sillewater]

Biochem Soc Trans. 2009 Aug;37(Pt 4):692-6.
Inhibitors of protein aggregation and toxicity.
Amijee H, Madine J, Middleton DA, Doig AJ.

Peptides directed for diagnosis and treatment of amyloid-associated diseases
United States Patent Application 20100022459

[VictorBjoerk]

Some interesting new stuff.



http://www.scienceda...00427111257.htm

Using a new mouse model of Alzheimer's disease, researchers at Mount Sinai School of Medicine have found that Alzheimer's pathology originates in amyloid-beta (Abeta) oligomers in the brain, rather than the amyloid plaques previously thought by many researchers to cause the disease.

[caston]

Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis.
http://www.ncbi.nlm....pubmed/12702875

[tunt01]

looks like the abeta hypothesis is focusing tightly on oligomers. i spent some time looking at this issue, and hopefully we can discuss this topic further.

- Oleocanthal in EVOO binds to ADDLs (oligomeric ligands) and changes their formation, inhibiting their ability to bind to synapses, improving neural function, and better allowing the body to remove them.
http://www.scienceda...90929133123.htm

- Iburofen supposedly functions in a similar matter to Oleocanthal. However, it's too bad we do not find a single Oleocanthal supplement. It might be smart for a supplement manufacturer to evaluate it.
- Improving lysosomal removal of oligomers would be an interesting possible idea (LysoSENS).
- Maintaining insulin sensitivity

- Curcumin may inhibit oligomers in vivo.
http://www.ncbi.nlm....pubmed/15590663
http://alzheimer.neu...u/Curcumin.html

- Clioquinol inhibits Abeta Oligomer assembly (Cliquinol was discussed as a life-span enhancing substance HERE.


we'll see what shakes out as the best solution, but there seems to be some pathways for those at risk of alzheimer's to pursue, and not just CR/exercise.


http://www.ncbi.nlm....pubmed/19664688

Edited by prophets, 30 April 2010 - 11:46 PM.

[AgeVivo]

my 2 cents, possibly out of scope: fast readings about rapamycin and clioquinol versus AD lead me to macroautophagy.

Review: autophagy and neurodegeneration: survival at a cost? http://www.ncbi.nlm....pubmed/20202120
Protein aggregation, mitochondrial impairment and oxidative stress are common to multiple neurodegenerative diseases. Homeostasis is regulated by a balanced set of anabolic and catabolic responses, which govern removal and repair of damaged proteins and organelles. Macroautophagy is an evolutionarily conserved pathway for the degradation of long-lived proteins, effete organelles and protein aggregates. Aberrations in macroautophagy have been observed in Alzheimer, Huntington, Parkinson, motor neuron and prion diseases. In this review, we will discuss the divergent roles of macroautophagy in neurodegenerative diseases and suggest a potential regulatory mechanism that could determine cell death or survival outcomes. We also highlight emerging data on neurite morphology and synaptic remodelling that indicate the possibility of detrimental functional trade-offs in the face of neuronal cell survival, particularly if the need for elevated macroautophagy is sustained.

Hope I'm not too much off-subject for people like prophets who are deeply studying the subject

[tunt01]

Hope I'm not too much off-subject for people like prophets who are deeply studying the subject

nah this is right on the money. lithium is probably another alternative. autophagy is critical. quite frankly, i think it's going to be interesting to see in the next 20-30 years which approach to treating AD becomes the best approach. is it upregulating autophagy for clearance? is it inhibiting the precursor formation/early steps?

maybe it will be a combination thereof and we should look at it as a multi-faceted solution (ie. sort of a life cycle approach).

Edited by prophets, 01 May 2010 - 03:40 PM.

[ken_akiba]

Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis.
http://www.ncbi.nlm....pubmed/12702875

fascinating.

[AgeVivo]

here is a AD-specialized miniforum for treatments that may be currently tested: http://alzheimers.in...frm/f/762104261

[tham]

"Yi Zhi" formula, based on rehmannia, ginkgo and cistanche.



http://www.chinabook...ds_to_display=1


http://www.ncbi.nlm....t_uids=10921161

http://www.ncbi.nlm....pubmed/18655563

http://www.ncbi.nlm....t_uids=19565731

http://www.ncbi.nlm....t_uids=12572375

http://www.ncbi.nlm....t_uids=12203266

http://www.ncbi.nlm....t_uids=10322856


On cistanche :

http://www.itmonline...s/cistanche.htm

http://en.wikipedia.org/wiki/Cistanche

Edited by tham, 06 May 2010 - 07:59 PM.

[tham]

PS, ALCAR, vinpocetine, ginkgo, bacopa monniera.

http://www.thorne.co...ext/4/3/144.pdf


Bacopa monniera.

http://findarticles....9/ai_114563492/



This MLM product combines ginkgo, bacopa and centella asiatica.

http://www.greatesth...kola_bacopa.htm

[tham]

Centella asiatica selectively decreases amyloid beta levels.

http://www.ncbi.nlm....t_uids=19048607

http://www.ncbi.nlm....t_uids=18431001