Why are we doing so little to prevent it?

Donepezil is plainly not the answer, but advances are indicating real protection (Prof David Smith Oxford)
He proved that in cases with high homocysteine levels,B12, folate and B6 showed clear protection.

I hope you can read the following!

Alzheimer’s disease is a physical disease which attacks the brain resulting in impaired memory, thinking and behaviour. The disease is named for the German physician, Alois Alzheimer who, in 1907, first described it.

As brain cells die, the substance of the brain shrinks. Abnormal material builds up as “tangles” in the centre of the brain cells and “plaques” outside the brain cells, disrupting messages within the brain, damaging connections between brain cells. This leads to the eventual death of the brain cells and prevents the recall of information.

Memory of recent events is the first to be affected, but as the disease progresses, long-term memory is also lost. The disease also affects many of the brain’s other functions and consequently, many other aspects of behaviour are disturbed.

There are two different types of Alzheimer’s disease:
Sporadic Alzheimer’s disease
# The disease can affect adults at any age, but usually occurs after age 65
# Sporadic Alzheimer’s disease is by far the most common form of Alzheimer’s disease
# It affects people who may or may not have a family history of the disease. Several competing hypotheses exist trying to explain the cause of the disease.
The oldest, on which most currently available drug therapies are based, is the cholinergic hypothesis, which proposes that AD is caused by reduced synthesis of the neurotransmitter acetylcholine. The cholinergic hypothesis has not maintained widespread support, largely because medications intended to treat acetylcholine deficiency have not been very effective.
Other cholinergic effects have also been proposed, for example, initiation of large-scale aggregation of amyloid, leading to generalised neuroinflammation.

In 1991, the amyloid hypothesis postulated that amyloid beta (A?) deposits are the fundamental cause of the disease.

Support for this postulate comes from the location of the gene for the amyloid beta precursor protein (APP) on chromosome 21, together with the fact that people with trisomy 21 (Down Syndrome) who have an extra gene copy almost universally exhibit AD by 40 years of age.
Also APOE4, the major genetic risk factor for AD, leads to excess amyloid buildup in the brain before AD symptoms arise. Thus, A? deposition precedes clinical AD.
Further evidence comes from the finding that transgenic mice that express a mutant form of the human APP gene develop fibrillar amyloid plaques and Alzheimer’s-like brain pathology with spatial learning deficits.

An experimental vaccine was found to clear the amyloid plaques in early human trials, but it did not have any significant effect on dementia. Researchers have been led to suspect non-plaque A? oligomers (aggregates of many monomers) as the primary pathogenic form of A?. These toxic oligomers, also referred to as amyloid-derived diffusible ligands (ADDLs), bind to a surface receptor on neurons and change the structure of the synapse, thereby disrupting neuronal communication.

One receptor for A? oligomers may be the prion protein, the same protein that has been linked to mad cow disease and the related human condition, Creutzfeldt-Jakob disease, thus potentially linking the underlying mechanism of these neurodegenerative disorders with that of Alzheimer’s disease.

In 2009, this theory was updated, suggesting that a close relative of the beta-amyloid protein, and not necessarily the beta-amyloid itself, may be a major culprit in the disease. The theory holds that an amyloid-related mechanism that prunes neuronal connections in the brain in the fast-growth phase of early life may be triggered by aging-related processes in later life to cause the neuronal withering of Alzheimer’s disease.

N-APP, a fragment of APP from the peptide’s N-terminus, is adjacent to beta-amyloid and is cleaved from APP by one of the same enzymes. N-APP triggers the self-destruct pathway by binding to a neuronal receptor called death receptor 6 (DR6, also known as TNFRSF21).
DR6 is highly expressed in the human brain regions most affected by Alzheimer’s, so it is possible that the N-APP/DR6 pathway might be hijacked in the aging brain to cause damage. In this model, beta-amyloid plays a complementary role, by depressing synaptic function.

A 2004 study found that deposition of amyloid plaques does not correlate well with neuron loss.
This observation supports the tau hypothesis, the idea that tau protein abnormalities initiate the disease cascade.
In this model, hyperphosphorylated tau begins to pair with other threads of tau. Eventually, they form neurofibrillary tangles inside nerve cell bodies.
When this occurs, the microtubules disintegrate, collapsing the neuron’s transport system. This may result first in malfunctions in biochemical communication between neurons and later in the death of the cells. Herpes simplex virus type 1 has also been proposed to play a causative role in people carrying the susceptible versions of the apoE gene.

Another hypothesis asserts that the disease may be caused by age-related myelin breakdown in the brain. Demyelination leads to axonal transport disruptions, leading to loss of neurons that become stale. Iron released during myelin breakdown is hypothesized to cause further damage. Homeostatic myelin repair processes contribute to the development of proteinaceous deposits such as amyloid-beta and tau.

Oxidative stress is a significant cause in the formation of the pathology.

AD individuals show 70% loss of locus coeruleus cells that provide norepinephrine (in addition to its neurotransmitter role) that locally diffuses from “varicosities” as an endogenous antiinflammatory agent in the microenvironment around the neurons, glial cells, and blood vessels in the neocortex and hippocampus.]
It has been shown that norepinephrine stimulates mouse microglia to suppress A?-induced production of cytokines and their phagocytosis of A?.[54] This suggests that degeneration of the locus ceruleus might be responsible for increased A? deposition in AD brains.
Pathophysiology
Main article: Biochemistry of Alzheimer’s disease
Histopathologic image of senile plaques seen in the cerebral cortex of a person with Alzheimer’s disease of presenile onset. Silver impregnation.
Neuropathology

Alzheimer’s disease is characterised by loss of neurons and synapses in the cerebral cortex and certain subcortical regions. This loss results in gross atrophy of the affected regions, including degeneration in the temporal lobe and parietal lobe, and parts of the frontal cortex and cingulate gyrus. Studies using MRI and PET have documented reductions in the size of specific brain regions in patients as they progressed from mild cognitive impairment to Alzheimer’s disease, and in comparison with similar images from healthy older adults.

Both amyloid plaques and neurofibrillary tangles are clearly visible by microscopy in brains of those afflicted by AD. Plaques are dense, mostly insoluble deposits of amyloid-beta peptide and cellular material outside and around neurons. Tangles (neurofibrillary tangles) are aggregates of the microtubule-associated protein tau which has become hyperphosphorylated and accumulate inside the cells themselves. Although many older individuals develop some plaques and tangles as a consequence of aging, the brains of AD patients have a greater number of them in specific brain regions such as the temporal lobe.[56] Lewy bodies are not rare in AD patient’s brains.
Biochemistry
Enzymes act on the APP (amyloid precursor protein) and cut it into fragments. The beta-amyloid fragment is crucial in the formation of senile plaques in AD.

Alzheimer’s disease has been identified as a protein misfolding disease (proteopathy), caused by accumulation of abnormally folded A-beta and tau proteins in the brain. Plaques are made up of small peptides, 39–43 amino acids in length, called beta-amyloid (also written as A-beta or A?).

Beta-amyloid is a fragment from a larger protein called amyloid precursor protein (APP), a transmembrane protein that penetrates through the neuron’s membrane. APP is critical to neuron growth, survival and post-injury repair. In Alzheimer’s disease, an unknown process causes APP to be divided into smaller fragments by enzymes through proteolysis. One of these fragments gives rise to fibrils of beta-amyloid, which form clumps that deposit outside neurons in dense formations known as senile plaques.
In Alzheimer’s disease, changes in tau protein lead to the disintegration of microtubules in brain cells.

AD is also considered a tauopathy due to abnormal aggregation of the tau protein. Every neuron has a cytoskeleton, an internal support structure partly made up of structures called microtubules. These microtubules act like tracks, guiding nutrients and molecules from the body of the cell to the ends of the axon and back. A protein called tau stabilizes the microtubules when phosphorylated, and is therefore called a microtubule-associated protein. In AD, tau undergoes chemical changes, becoming hyperphosphorylated; it then begins to pair with other threads, creating neurofibrillary tangles and disintegrating the neuron’s transport system.
Disease mechanism

Exactly how disturbances of production and aggregation of the beta amyloid peptide gives rise to the pathology of AD is not known. The amyloid hypothesis traditionally points to the accumulation of beta amyloid peptides as the central event triggering neuron degeneration. Accumulation of aggregated amyloid fibrils, which are believed to be the toxic form of the protein responsible for disrupting the cell’s calcium ion homeostasis, induces programmed cell death (apoptosis). It is also known that A? selectively builds up in the mitochondria in the cells of Alzheimer’s-affected brains, and it also inhibits certain enzyme functions and the utilisation of glucose by neurons.

Various inflammatory processes and cytokines may also have a role in the pathology of Alzheimer’s disease. Inflammation is a general marker of tissue damage in any disease, and may be either secondary to tissue damage in AD or a marker of an immunological response.[67]

Alterations in the distribution of different neurotrophic factors and in the expression of their receptors such as the brain derived neurotrophic factor (BDNF) have been described in AD.
Note that BDNF increases with physical exercise.
Genetics

The vast majority of cases of Alzheimer’s disease are sporadic, meaning that they are not genetically inherited although some genes may act as risk factors. On the other hand, around 0.1% of the cases are familial forms of autosomal-dominant inheritance, which usually have an onset before age 65.

Most of autosomal dominant familial AD can be attributed to mutations in one of three genes: amyloid precursor protein (APP) and presenilins 1 and 2.

Most mutations in the APP and presenilin genes increase the production of a small protein called A?42, which is the main component of senile plaques.
Some of the mutations merely alter the ratio between A?42 and the other major forms—e.g., A?40—without increasing A?42 levels. This suggests that presenilin mutations can cause disease even if they lower the total amount of A? produced and may point to other roles of presenilin or a role for alterations in the function of APP and/or its fragments other than A?.

Most cases of Alzheimer’s disease do not exhibit autosomal-dominant inheritance and are termed sporadic AD. Nevertheless genetic differences may act as risk factors.

The best known genetic risk factor is the inheritance of the ?4 allele of the apolipoprotein E (APOE). Between 40 and 80% of patients with AD possess at least one apoE4 allele. The APOE4 allele increases the risk of the disease by three times in heterozygotes and by 15 times in homozygotes. Geneticists agree that numerous other genes also act as risk factors or have protective effects that influence the development of late onset Alzheimer’s disease. Over 400 genes have been tested for association with late-onset sporadic AD, most with null results.

Apolipoprotein E, type ?4 allele (APOE ?4), is associated with late-onset familial Alzheimer’s disease (AD). There is high avidity and specific binding of amyloid ?-peptide with the protein ApoE. To test the hypothesis that late-onset familial AD may represent the clustering of sporadic AD in families large enough to be studied, we extended the analyses of APOE alleles to several series of sporadic AD patients. APOE ?4 is significantly associated with a series of probable sporadic AD patients (0.36 ± 0.042, AD, versus 0.16 ± 0.027, controls [allele frequency estimate ± standard error], p = 0.00031). Spouse controls did not differ from CEPH grandparent controls from the Centre d’Etude du Polymorphisme Humain (CEPH) or from literature controls. A large combined series of autopsy-documented sporadic AD patients also demonstrated highly significant association with the APOE ?4 allele (0.40 ± 0.026, p ? 0.00001). These data support the involvement of ApoE ?4 in the pathogenesis of late-onset familial and sporadic AD. ApoE isoforms may play an important role in the metabolism of ?-peptide, and APOE ?4 may operate as a susceptibility gene (risk factor) for the clinical expression of AD.

MAJOR PROTECTIVE STRATEGIES
Reverse risk factors for vascular disease.
CORRECT nutritional deficiencies.
(1) Optimize minerals , making sure that copper is not high and that there is no excess of lead, mercury or heavy metals.
(2) Bring B12 to at least 700 pmol/l, folic acid to at least 35 nmol/L, homocysteine to 8umol/L or less.
(3) Optimize vitamin 25D3 to at least 80 nmol/L
(4) Reverse insulin resistance (insulin at 1 hour after meal should be less than 40mU/L, while normalizing glucose and triglycerides, but not over-lowering LDL cholesterol.
(5) Consume sufficient branch chain amino acids (eggs and whey protein)
(6) Omega 3 fatty acids at more than 10ml/day.

ADD PROTECTIVE PLANT SUBSTANCES
(1) Turmeric at one and a half teaspoons twice per day (with black pepper to enhance absorption and prolong half life)(or curcumin 200mg tds with about 20 mg piperine per dose)
(2) Resveratrol 200mg bd
(3) Coenzyme Q10 150 mg daily (as mixed ubiquinone and ubiquinol)
The piperine above will enhance Q10 absorption.
(4) R alpha lipoic acid 100mg tds
(5) Acetyl l-carnitine 500mg bd
(6) Antioxidants, especially berry plants,(anthocyanosides and proanthocyanidins) and dark green vegetables (lutein, zexanthin,vitamin K)
(7) Cocoa flavanoids
(8) Include more raw and fresh food, including plenty of vitamin C.
PREVENT GLYCATION AND CARBONYLATION OF PROTEINS,
Control Glucose levels and use l-carnosine.
ADD PHYSICAL EXERCISE AT LEAST 20 MINUTES TWICE DAILY!
Do mind activities to increase mental diversity.)(Crosswords, sudoku, quizzes etc)
Meditate
Listen to good music every day.
Engage in conversation with interesting people

As investigators studied this newly-discovered nutrient, found in many foods such as tofu, green tea and spinach, it became apparent that PQQ was essential for good health. But it wasn’t until 2003 that Japanese scientists discovered its biochemical role in the lysine degradation process, and proposed it may belong to the B vitamin complex.(1)

PQQ and Mitochondrial Health

Mitochondria are the energy producers of the cells. They work much like the engine of a car. What is a car without its engine? Just a big, inert hunk of metal. Similarly, without mitochondria, the cells in your body would not be able to do anything. Your heart would not beat; your lungs would not breathe; your brain would cease to function. Mitochondria are essential to life itself.

As you might expect, since proper mitochondrial function is so critical for health and life, mitochondrial dysfunction plays a significant part in many types of illnesses, including fibromyalgia, chronic fatigue syndrome (ME/CFS), type 2 diabetes, heart failure, Alzheimer’s and Parkinson’s disease. And many cell biologists believe the quantity and function of mitochondria are key determinants of longevity.(2–4)

Now you’re probably wondering what PQQ has to do with our mitochondria. As it turns out, quite a lot.

A series of in-vivo studies found that when mice are deprived of dietary PQQ, they have fewer mitochondria in their tissues. They also exhibited stunted growth, compromised immunity, and impaired reproductive capability. In addition, the survival rates of juvenile mice were significantly reduced in the absence of PQQ.(5–7)

Why is PQQ so important for mitochondrial health? Because our mitochondria are extremely vulnerable to damage and destruction from free radicals, and PQQ is a super-powerful antioxidant with formidable free-radical scavenging capabilities. It is also an exceptionally stable molecule that is able to do its work successfully without breaking down.

According to a University of California at Davis study, PQQ is 30 to 5,000 times more efficient in sustaining mitochondrial energy production than the other common antioxidant compounds most people rely on, like ascorbic acid.(8)

If you think PQQ’s ability to support and protect existing mitochondria sounds impressive, just wait — PQQ is able to perform an even more impressive feat.

In 2010, researchers discovered that PQQ actually stimulates mitochondrial biogenesis — the growth of fresh, new mitochondria! (9)

This was a huge discovery. Up until then, the only natural ways known to stimulate the growth of new mitochondria were long-term and sustained calorie restriction or strenuous physical activity — both of which were far too rigorous and impractical for most aging or ill individuals.

Supporting Reversal of Cognitive Decline

As we get older, most of us start experiencing some memory loss and cognitive functioning difficulties — evidence of the increased toll free radicals and oxidative stress are taking on our mitochondria. In one study, researchers found evidence of 50% more mitochondrial damage in the brain cells of people over 70 compared to those in middle-aged individuals.(10)

Although that finding was not encouraging, there is good news. According to a 2007 scientific review in Current Opinion in Clinical Nutrition & Metabolic Care, age-related mitochondrial dysfunction can be reversed.(11)

When it comes to improving cognitive function and reversing mitochondrial dysfunction, PQQ and CoQ10 could aptly be called the dynamic duo.

While CoQ10 works to support optimum mitochondrial function, PQQ is busy encouraging the activation of genes that trigger mitochondrial reproduction, protection and repair.

A 2009 clinical trial in Japan clearly demonstrated this synergy. Middle-aged and elderly people who were given 20 mg per day of PQQ showed improvement in tests of higher cognitive function. However, the improvements were significantly amplified when the subjects also took 300 mg of CoQ10 each day. The researchers concluded that 20 mg of PQQ plus 300 mg of CoQ10 daily may support reversal of age-related cognitive decline in aging humans.(12)

Neuroprotective Effect in Alzheimer’s and Parkinson’s Diseases

Mitochondrial dysfunction is thought to be linked to age-related diseases like Alzheimer’s and Parkinson’s. And an increasing body of evidence indicates that PQQ may be an effective intervention for Alzheimer’s disease and Parkinson’s disease.

Both diseases are triggered by an accumulation of abnormal proteins which initiate a cascade of oxidative damage that results in brain cell death. Studies have revealed that PQQ helps the body to:

* Prevent development of the protein alpha-synuclein, which is associated with Parkinson’s disease.(13)

* Prevent the formation of amyloid-beta molecular structures associated with Alzheimer’s disease.(14)

* Protect nerve cells from the oxidizing ravages of the amyloid-beta protein linked with Alzheimer’s disease.(15)

PQQ — Looking to the Future

It appears that scientists are just beginning to scratch the surface of the benefits PQQ may provide. In several animal studies, PQQ has shown great promise in supporting a reduction of the damage from heart attack, stroke and spinal cord injury.

For example, a 2006 study using rats actually found PQQ to be superior to the well known prescription beta-blocker metoprolol in supporting reduced oxidative damage after a heart attack. Supplementation with PQQ was associated with a reduced area of cardiac tissue death and improved overall cardiac function.(16)

It’s going to be exciting to watch and see what other as-yet-unknown health benefits PQQ may hold.

ProHealth’s ProMito PQQ™

ProMito PQQ is a unique nutrient blend which combines PQQ with Alpha GPC (alpha glycerylphosphorylcholine) to support enhanced memory retention and promote improved mental processing.

Alpha GPC is a pro-phospholipid that delivers the essential nutrient choline to the brain. A meta-analysis of 10 clinical trials evaluating Alpha GPC and its effectiveness in helping dementia-related symptoms found that patients taking Alpha GPC had consistently improved scores on a wide variety of memory and attention span tests.(17)

In short, numerous studies suggest these two novel ingredients — PQQ and Alpha GPC — promote improved neurological health, improved memory retention and mental acuity. A benefit that may be enhanced by a daily regimen that also includes coenzyme Q10.

Each veggie capsule of ProHealth ProMito PQQ contains 20 mg PQQ and 50 mg Alpha GPC. One capsule per day should be sufficient for most purposes, or as advised by your healthcare professional. No adverse side effects are known when it is used appropriately.

Summary

PQQ is an essential nutrient that not only protects and defends our existing mitochondria but is also able to stimulate the growth of fresh new mitochondria. Numerous studies have demonstrated PQQ’s ability to support a reversal of cognitive decline and promote improved memory, concentration and mental alertness, especially when taken with coenzyme Q10.

(24) Conspicuous absence.Is something missing?
What could have been overlooked?
(25) Systems thinking. Identify belief systems in family and friends.
(26) Visiting developmental levels.
(27) Wilber’s four quadrants
(28) Exploring creativity.
(29) Re-explore resources
(30) Ecological checking.
Are solutions congruent with person’s goals and hopes?
(30) Practicing new learnings and repertoires.Relate them to contexts.

My sun shall rise in the East; so shall my heart be at peace.
And if you’re asking me when, I’ll say it starts at the end.
You know your will to be free is matched with love secretly.
And talk will alter your prayer; somehow you’ll find you are there.

Your friend is close by your side and speaks in far ancient tongue.
A season’s wish will come true: All seasons begin with you.
The world we all come from: one world we melt into one.
Just hold my hand and we’re there.
Somehow we’re going somewhere.

You ask me where to begin? Am I so lost in my sin?
You ask me where did I fall? I’ll say I can’t tell you when.
But if my spirit is strong, I’ll know it can’t be long.
No question, I’m not alone: somehow I’ll find my way home!

Vangelis

In all of the vast cosmos, this planet is the only place that we know can support our kind of life.
Since life has developed in profound coordination with the domain of its existence, it is appropriate to have near total confidence that nature has evolved diverse mechanisms that support complex living systems, with a peak at the human complexity of an organism with multi-trillions of coordinated cells, and a brain with 100 billion nerve cells and up to 100 trillion synaptic connections.
At last we have arrived in language and can ask ”Who speaks for earth?”
Who are we, that might be on the threshold of explaining ourselves to ourselves?
A requirement is a capacity to grasp bigger pictures, and this involves ecology of mind as well as coordination with the healthiest ecologies in nature.
What a key word is the term “coordination”, when we realize that these systems are in fact cybernetic.
That is, there are” coordinations of coordinations.”
The feedback and feed forward processes have understandable mechanisms for these regulations.
Epigenetics is a splendid illustration of this
There is a very interesting lecture on “New biology”, by Prof Bruce Lipton, and it can be found through Google.
His models make it much clearer about the function of protein folding and the swinging ends as electrical charges are made.
Thus the cell itself can determine whether genes are activated or silenced, by the signals that operate on the epigenetic marker regions of these histones wound around gene structures.(see enclosed diagrams)
It is fascinating to see what will emerge in terms of the so called non coding DNAs, which code for RNAs that do not code for protein, but are still like switches in gene coordinations.
Human genes occupy about 2% of our DNA, and the” non-coding” region is the remaining 98%!
Are histones signal receivers here as well?
The close cell to cell talk, the genes that code for cytokine receptors will also change according to what environmental chemicals (good and bad) do to the histone epigenetic receptors.
But more remote cybernetic happenings are likely to be result as well (eg in the hyperinsulinaemic, insulin resistant person responding for example to high fructose intake.

Living systems are amazingly specific in their within cell, cell to cell, organ to organ, and even brain activations and recursions,as elaborate patterns.

Thus mind to mind via language requires great attention to meanings of words and grasping of metaphors.
Never has it been more important to understand how we came to our ideas and explanations as well as asking each other to elaborate on whatever is under discussion.
So here I am writing about John’s version of this subject!

John G

Please send emails to Prime Minister, Peter O’Neill, and Deputy Prime Minister and Forest Minister, Belden Namah, calling on them to suspend the logging until on-going investigations have been completed.

An existing Commission of Inquiry into the leases has already uncovered systemic problems including fraud, forgery and a failure to secure the informed consent of traditional owners. [1]

But the leases have been used to secure Forest Clearance Authorities that allow the clear-felling of 2 million hectares of forest within the lease areas.

If the leases are unlawful because proper processes have not been followed and traditional owners have not given their informed consent, then the logging is also illegal.

Traditional landowners are mounting their own protests against the logging but they need your help as their protests are being met with violence [2].

The term for the Commission of Inquiry has just been extended by 5 months [3] to allow a full investigation of all the issues and regional hearings — but while the Commission process grinds on the logging is continuing unabated, causing irreversable environmental damage, mounting community tensions [4] and human rights abuses [5].

The government must immediately suspend all Forest Clearance Authorities until the Commission of Inquiry has been completed and its recommendations implemented.