Has Stanford University found a cure for Alzheimer's disease?

[JPV]

Not sure if this is entirely relevant to CFS/ME but it involves modifying microglial activity, which I know is discussed a lot on the forum, so I thought there might be something of interest here...

Has Stanford University found a cure for Alzheimer's disease?
A drug which boosts the brain's immune response may prevent or cure Alzheimer's disease, scientists believe

Alzheimer's could be prevented and even cured by boosting the brain's own immune response, scientists at Stanford University believe.

Researchers discovered that nerve cells die because cells which are supposed to clear the brain of bacteria, viruses and dangerous deposits, stop working.

These cells, called 'microglia' function well when people are young, but when they age, a single protein called EP2 stops them operating efficiently.

Now scientists have shown that blocking the protein allows the microglia to function normally again so they can hoover up the dangerous sticky amyloid-beta plaques which damage nerve cells in Alzheimer's disease.

The researchers found that, in mice, blocking EP2 with a drug reversed memory loss and myriad other Alzheimer’s-like features in the animals.

“Microglia are the brain’s beat cops,” said Dr Katrin Andreasson, Professor of neurology and neurological sciences at Stanford University School of Medicine.

 

[lansbergen]

http://en.wikipedia.org/wiki/Prostaglandin_E2_receptor

Prostaglandin E2 receptor (53kDa), also known as EP2, is a prostaglandin receptor for prostaglandin E2.

 

[cigana]

Interesting. On a similar theme, Dr Alan MacDonald has performed autopsies showing that Borrelia DNA is found in those plaques and since Borrelia is known to produce biofilm he hypothesises Lyme can cause Alzheimers.
(see eg. http://www.spirochaetalalzheimersassociation.org/launchmtg.html)

 

[cigana]

http://en.wikipedia.org/wiki/Prostaglandin_E2_receptor

Prostaglandin E2 receptor (53kDa), also known as EP2, is a prostaglandin receptor for prostaglandin E2.

Does that mean prostaglandin E2 could be raised in people with too much EP2 ?

 

[lansbergen]

Does that mean prostaglandin E2 could be raised in people with too much EP2 ?

As I understand it EP2 is the receptor for prostaglandin E2

 

[anciendaze]

Since the type of spirochete found in Alzheimer's brains is not always the same, it is possible neuroborreliosis is due to impaired immune function in the brain.

Also, the problem is likely to be different than "too much" or "too little" immune activity. There are good reasons to think misdirected immune response is behind "autoinflammatory" and "autoimmune" diseases.

 

[Bob]

@JPV, thanks for posting.

If ME patients have over-active microglia, then it would be interesting to know how ME patients compare with the rest of the population in terms of the proportion who are vulnerable to alzheimer's. Our microglia might be over-active but dysfunctional, so the differences in alzheimer's prevalence between ME patients and the rest of the population might be subtle or counter-intuitive. And any possible dysfunction of microglia in alzheimer's might affect ME patients the same as everyone else. Interesting to explore.

 

[Valentijn]

http://en.wikipedia.org/wiki/Prostaglandin_E2_receptor

Prostaglandin E2 receptor (53kDa), also known as EP2, is a prostaglandin receptor for prostaglandin E2.

I don't know about EP2, but a lot of KDM's patients have been testing quite high for PGE2.

 

[Valentijn]

Does that mean prostaglandin E2 could be raised in people with too much EP2 ?

I don't think so. But it could mean that too much PGE2 is just as bad as too much EP2. Since EP2 is a receptor, it typically wouldn't be doing much without PGE2 to kick it into action.

So extra EP2 could trigger activation of something, since more of it would mean that it's hooking up with PGE2 more often. And extra PGE2 could potentially have the same effect, if hooking up with normal amounts of EP2 more often.

I think it really depends on the exact mechanism. Is the EP2, as a receptor, somehow directly preventing microglia from doing their job? Or is the EP2, in the process of being activated by PGE2, triggering a response a bit further along, which then interferes with the microglia?

 

[cigana]

I don't think so. But it could mean that too much PGE2 is just as bad as too much EP2. Since EP2 is a receptor, it typically wouldn't be doing much without PGE2 to kick it into action.

So extra EP2 could trigger activation of something, since more of it would mean that it's hooking up with PGE2 more often. And extra PGE2 could potentially have the same effect, if hooking up with normal amounts of EP2 more often.

I think it really depends on the exact mechanism. Is the EP2, as a receptor, somehow directly preventing microglia from doing their job? Or is the EP2, in the process of being activated by PGE2, triggering a response a bit further along, which then interferes with the microglia?

Interesting, thanks.
I mention this because in most of the test reports I've seen from KDM's patients, PGE2 is raised. It seems to be quite common.
EDIT: Just saw you mentioned the same thing Valentijn

 

[alex3619]

http://en.wikipedia.org/wiki/Prostaglandin_E2_receptor

Prostaglandin E2 receptor (53kDa), also known as EP2, is a prostaglandin receptor for prostaglandin E2.

Which has been implicated one way or another in CFS since at least 1993. I was a subject in some of the early research, much of which went unpublished. This ties in to inflammation, changes in diet, salicylate intolerance, glutathione deficiency and increased nitric oxide.

 

[snowathlete]

There are, as I understand it, four different prostaglandin receptors and it's the receptors rather than the PGE2 itself that determin what it does when it interacts with the receptor.

As others have said, PGE2 appears to be high in ME/CFS. Mine is sky high and is a major part of my focus at the moment. It is driven by COX-2.

It's complex and needs proper attention from researchers. I have been reaching the conclusion lately that it could well be really important in understanding what's going on in ME/CFS.

 

[SDSue]

Which has been implicated one way or another in CFS since at least 1993. I was a subject in some of the early research, much of which went unpublished. This ties in to inflammation, changes in diet, salicylate intolerance, glutathione deficiency and increased nitric oxide.

Alex, was it drug trials or simply looking for markers? I assume it led to a dead end and the researchers changed direction?

 

[alex3619]

Not even close. It died from lack of funding and from the doctor involved being pressured into getting out of CFS treatment and research. There were about five published papers, but only one was indexed on pubmed:

Eicosanoids and essential fatty acid modulation in chronic disease and the chronic fatigue syndrome.
Gray JB, Martinovic AM.

Erratum in

• Med Hypotheses 1995 Aug;45(2):219.

Abstract
Abnormalities of Essential Fatty Acid (EFA) incorporation into phospholipid are found in chronic diseases. More recently changes in circulating EFA metabolites (EFAM) together with EFAM hypo-responsiveness of immune cells and EFAM production from cells have been found associated with disease. We hypothesize that changes in ratio of EFAMs are the normal physiological responses to stressors, but when stressors are excessive or prolonged, EFAM systems may become unpredictably hypo-responsive owing to factors such as receptor down regulation and substrate depletion. In time, many homeostatic system become deranged and held in that state by minor stressors. Literature review of chronic fatigue syndrome (CFS) shows hyper and hypo-responsiveness in immune function, several Hypothalamo-Pituitary (HP) axes and sympathetic nervous system, all relatable to dysfunctional changes in EFA metabolism. For the first time, we explain chronic immune system activation and hypo-responsive immune function in CFS; through EFAMs. Dietary EFA modulation (DEFA) can alter ratios of both membrane EFAs and produced EFAMs, and if maintained can restore hypo-responsive function. We discuss dietary strategies and relevance in CFS, and a case series of CFS patients applying DEFA with other titrated published managements which saw 90% gaining improvement within 3 months and more than 2/3 fit for full time duties. This hypothesis and DEFA may have relevance in other chronic conditions.

PMID: 7968718

Dr Martinovic's surgery was just around the corner from where I was living while I was studying computer science.

 

[ahmo]

Alzheimer's could be prevented and even cured by boosting the brain's own immune response

Low dose naltrexone??


@JPV Your avatar is so graphic. I feel myself mirroring him everytime I see it. Happy New Year to you.

 

[SDSue]

Not even close. It died from lack of funding and from the doctor involved being pressured into getting out of CFS treatment and research. There were about five published papers, but only one was indexed on pubmed:

Yikes! Makes one wonder how many other relevant studies were shoved aside and how many good scientists have been pressured out of the ME/CFS field. Hopefully the tide Is turning ? thanks to some very brave physicians and advocates!

 

[beaker]

Blocking receptor in brain’s immune cells counters Alzheimer’s in mice, study finds
{Stanford's Newsletter}

Epidemiological reports suggest that the use of nonsteroidal anti-inflammatory drugs, such as aspirin, can prevent the onset of Alzheimer’s — although only if their use is initiated well before any signs of the disorder begin to show up in older people, Andreasson said. “Once you have any whiff of memory loss, these drugs have no effect,” she said. NSAIDs’ mainly act by blocking two enzymes called COX-1 and COX-2; these enzymes create a molecule that can be converted to several different substances, including PGE2 — the hormone-like chemical that triggers EP2 action.

Although PGE2 is known to regulate inflammatory changes in the brain, it exercises diverse, useful functions in different tissues throughout the body, from influencing blood pressure to inducing labor. Complicating matters, PGE2 is just one of five different prostaglandins originating from the precursor molecule produced by COX-1 and COX-2. So aspirin and other COX-1- and COX-2-inhibiting drugs may have myriad effects, not all of them beneficial. It may turn out that a compound blocking only EP2 activity on microglial cells, or some downstream consequences within microglial cells, would be better-suited for fending off Alzheimer’s without side effects, said Andreasson. Meanwhile, her group is exploring the biological mechanisms via which PE2 signaling pushes microglia over to the dark side.

 

[beaker]

Wonder if they are looking at the compounds studied at Emory.
New class of potential drugs inhibits inflammation in brain

I guess it's easy to get lost thinking one can find some wonderful overlooked med to try.
But as they say: Hope springs eternal. ;-)

 

[alex3619]

There are a LOT more than five substances by the way. Maybe hundreds. By five they mean a specific subtype - in this case series 2 prostaglandins. Even then its a pickle because series 3 prostaglandins will also be affected, and these drugs may cause a biochemical shunt into PGE1 and possibly other substances.

 

[heapsreal]

Many ssri's and other antidepressants are prescribed in many neurological conditions even if depression is present or not. I know many with cfs/me have cant tolerate them. But i think one of the main reasons they are prescribed by neurologists is because they do have anti inflammatory effects eg lowering tnf alpha and other cytokines. ALso neurogenesis is also an important factor in neurological disorders too.

Another med used in alzheimers is memantine which is an nmda antagonist and also reduces many inflammatory cytokines. Also neurogenesis from memantine.

Something else i have been looking into is high doses of melatonin 20mg which has shown to have immune modulating effects which i think are through its anti inflammatory effects.

Progression of alot of neurological disorders seems to come down to increasing inflammation. I wonder if a combination would work better for cfs/me. The pridgen study results will be interesting but i wonder if other anti inflammatories were added to the nsaids if improvement could be improved upon, attack the inflammation from different angles and different cytokines.

I am considering a small shot gun approach to this, low dose ssri/lexapro 5mg, memantine 5-10mg, melatonin 20mg nightly, naproxen at night has helped my neuropathy along with lyrica, also on dhea replacement which also has anti inflammatory effects. Probably a few other items im on that also have anti inflammatory effects as secondary actions? But need to do a bit more digging around first.