There are some interesting novel treatment approaches to the treatment of Alzheimer's, but they seem to be preliminary. Still, they do seem promising:
Adenosine(Specifically A2A) receptor antagonists not only improve symptoms, but actually prevent Amyloid beta neurotoxicity:
Alzheimer’s disease (AD) is a neurodegenerative disorder of the central nervous system manifested by cognitive and memory deterioration, a variety of neuropsychiatric symptoms, behavioral disturbances, and progressive impairment of daily life activities. Current pharmacotherapies are restricted to symptomatic interventions but do not prevent progressive neuronal degeneration. Therefore, new therapeutic strategies are needed to intervene with these progressive pathological processes. In the past several years adenosine, a ubiquitously released purine ribonucleoside, has become important for its neuromodulating capability and its emerging positive experimental effects in neurodegenerative diseases. Recent research suggests that adenosine receptors play important roles in the modulation of cognitive function. The present paper attempts to review published reports and data from different studies showing the evidence of a relationship between adenosinergic function and AD-related cognitive deficits. Epidemiological studies have found an association between coffee (a nonselective adenosine receptor antagonist) consumption and improved cognitive function in AD patients and in the elderly. Long-term administration of caffeine in transgenic animal models showed a reduced amyloid burden in brain with better cognitive performance. Antagonists of adenosine A2A receptors mimic these beneficial effects of caffeine on cognitive function. Neuronal cell cultures with amyloid beta in the presence of an A2A receptor antagonist completely prevented amyloid beta-induced neurotoxicity. These findings suggest that the adenosinergic system constitutes a new therapeutic target for AD, and caffeine and A2A receptor antagonists may have promise to manage cognitive dysfunction in AD.
Source: http://www.ncbi.nlm....les/PMC2769004/
Caffeine would also be the safest adenosine antagonist, but more powerful and selective ones could be considered(Although their safety profile is kinda shady)
Cannabinoids are also an interesting therapeutic approach, as they seem to reduce inflammation and beta-Amyloid neurotoxicity, even in non-psychoactive doses:
Alzheimer's disease is an age-related neurodegenerative condition associated with cognitive decline. The pathological hallmarks of the disease are the deposition of β-amyloid protein and hyperphosphorylation of tau, which evoke neuronal cell death and impair inter-neuronal communication. The disease is also associated with neuroinflammation, excitotoxicity and oxidative stress. In recent years the proclivity of cannabinoids to exert a neuroprotective influence has received substantial interest as a means to mitigate the symptoms of neurodegenerative conditions. In brains obtained from Alzheimer's patients alterations in components of the cannabinoid system have been reported, suggesting that the cannabinoid system either contributes to, or is altered by, the pathophysiology of the disease. Certain cannabinoids can protect neurons from the deleterious effects of β-amyloid and are capable of reducing tau phosphorylation. The propensity of cannabinoids to reduce β-amyloid-evoked oxidative stress and neurodegeneration, whilst stimulating neurotrophin expression neurogenesis, are interesting properties that may be beneficial in the treatment of Alzheimer's disease. Δ9-tetrahydrocannabinol can also inhibit acetylcholinesterase activity and limit amyloidogenesis which may improve cholinergic transmission and delay disease progression. Targeting cannabinoid receptors on microglia may reduce the neuroinflammation that is a feature of Alzheimer's disease, without causing psychoactive effects. Thus, cannabinoids 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. The evidence supporting a potential role for the cannabinoid system as a therapeutic target for the treatment of Alzheimer's disease will be reviewed herewith.
Source: http://www.ncbi.nlm....les/PMC2190031/
Oregano and many other herbs contains beta-caryophyllene, a cannabinoid that is a selective agonist for CB2 receptors. Perhaps you could incorporate that(Oregano and other herbs that contain this chemical) into your stack?
Another interesting and promising avenue of treatment is increasing norepinephrine levels. Animal studies have shown to reduced Norepi levels reduces beta-Amyloid clearance and negatively impacts cognition. Reduced NE levels are also linked to neuroinflammation in Alzheimer's. Restoring Norepi levels not only reverses a lot of inflammation and cognitive decline, but actually slow the progression of the disease:
The Alzheimer's disease (AD) epidemic is a looming crisis, with an urgent need for new therapies to delay or prevent symptom onset and progression. There is growing awareness that clinical trials must target stage-appropriate pathophysiological mechanisms to effectively develop disease-modifying treatments. Advances in AD biomarker research have demonstrated changes in amyloid-beta (Aβ), brain metabolism and other pathophysiologies prior to the onset of memory loss, with some markers possibly changing one or two decades earlier. These findings suggest that amyloid-based therapies would optimally be targeted at the earliest clinically detectable stage (such as mild cognitive impairment (MCI)) or before. Postmortem data indicate that tau lesions in the locus coeruleus (LC), the primary source of subcortical norepinephrine (NE), may be the first identifiable pathology of AD, and recent data from basic research in animal models of AD indicate that loss of NE incites a neurotoxic proinflammatory condition, reduces Aβ clearance and negatively impacts cognition - recapitulating key aspects of AD. In addition, evidence linking NE deficiency to neuroinflammation in AD also exists. By promoting proinflammatory responses, suppressing anti-inflammatory responses and impairing Aβ degradation and clearance, LC degeneration and NE loss can be considered a triple threat to AD pathogenesis. Remarkably, restoration of NE reverses these effects and slows neurodegeneration in animal models, raising the possibility that treatments which increase NE transmission may have the potential to delay or reverse AD-related pathology. This review describes the evidence supporting a key role for noradrenergic-based therapies to slow or prevent progressive neurodegeneration in AD. Specifically, since MCI coincides with the onset of clinical symptoms and brain atrophy, and LC pathology is already present at this early stage of AD pathogenesis, MCI may offer a critical window of time to initiate novel noradrenergic-based therapies aimed at the secondary wave of events that lead to progressive neurodegeneration. Because of the widespread clinical use of drugs with a NE-based mechanism of action, there are immediate opportunities to repurpose existing medications. For example, NE transport inhibitors and NE-precursor therapies that are used for treatment of neurologic and psychiatric disorders have shown promise in animal models of AD, and are now prime candidates for early-phase clinical trials in humans.
Source: http://www.ncbi.nlm....pubmed/23634965
To go along with this, dopamine-beta-hydroxylase(the enzyme that converts dopamine to norepinephrine) has been shown to be reduced in people with AD postmortem(http://www.ncbi.nlm....ubmed/6779929).
Stimulants(Norepi Reuptake Inhibitors and Releasing agents), especially amphetamine, might be useful for this short term. But long term, sustainable treatment, would probably be trying to restore function of dopamine-beta-hydroxylase and/or norepinephrine precursor therapy.
Norepinephrine precursors like L-tyrosine and L-Dopa first convert to dopamine, then dopamine is broken down into norepinephrine. So perhaps precursors are not the best of ideas. The main focus should then be upregulation of dopamine-beta-hydroxylase:
Corticosterone upregulates dopamine-beta-hydroxylase and norepinephrine transporters in rats: http://www.ncbi.nlm....les/PMC3924588/
Nitric Oxide induces long term upregulation of not only dopamine-beta-hydroxylase, but all catecholamine producing enzymes(tyrosine hydroxylase etc.): http://www.ncbi.nlm....pubmed/12645083
So, then we should be looking for supplements that boost nitric oxide, and L-arginine(http://www.ncbi.nlm..../pubmed/8769510) would be the best for this purpose. However nitric oxide is a powerful vasodilator, and too much can cause hypotension.
This is all theoretical, but it could be interesting if you add in a little bit of Caffeine, Oregano and L-arginine into your stack and see if it helps.
Edited by β-Endorphin, 12 March 2015 - 06:19 PM.
