Junk food and Alzheimer's

[Bartelby]

A large body of evidence now suggests that Alzheimer's is primarily a metabolic disease. Some scientists have gone so far as to rename it: they call it type 3 diabetes.

New Scientist carried this story on its cover on 1 September

Anybody read the NS article?

[ollinger]

I read it, and it doesn't represent a large body of thought in Alzheimer's research. (I was part of the group at Mt. Sinai that did some of the earliest work on Tacrine, the first drug approved to treat Alzheimers, a cholinesterase inhibitor since supplanted by Aricept, Exelon and Razadyne which have fewer side effects. I've been twice board certified in geriatric psychiatry. I know of what I speak). It's not even clear that the dementia associated with metabolic syndrome is Alzheimer's; it may be vascular, or multi-infarct type, which can be symptomatically identical. The most active areas of research in Alzheimer's currently concern the effects of amyloid accumulation and perhaps more importantly tau protein accumulation. The insulin receptor research is not currently considered very promising and any hysteria about a connection between Alzheimer's and junk food at this juncture has to be considered a bit juvenile, though it makes a nice story in quasi-scientific magazines.

[r2473]

Did I go to McDonalds this evening?

I can't remember.

[Bartelby]

Yes, well, I only had to register and it was free.

It does sound a bit too new and speculative, but ten years from now and more research ...


A better understanding of this process might come from Craft's next project; she has just been awarded $7.9 million by the US National Institutes of Health in Bethesda, Maryland, to test the nasal insulin spray on 240 volunteers showing signs of dementia. Teams across the US will monitor learning, memory, daily function and any brain changes using PET scans.

[ollinger]

We'll keep our fingers crossed. Nothing available now is very helpful for Alzheimer's. There are at least two drugs in trial now, I believe one in Japan and one in Sweden, that apparently both scavenge and reduce the tau protein that accumulates in Alzheimer brains. Initial uncontrolled studies suggested they possibly halted the progression of the disease; results of the controlled trials are due in the next year or two.

[charliefedererer]

There was a very promising study in Nature last month, "A mutation in APP protects against Alzheimer’s disease and age-related cognitive decline"

It had been noted that Alzheimer's disease was rare in Iceland.

A team of scientists have actually found a gene mutation that protects against the development of Alzheimer's.

It has long been known that the brain cells of patients with Alzheimer's contain large amounts of an abnormal protein known as amyloid beta.

This discovery leads to a better understanding of how amyloid beta is responsible for Alzheimer's, and gives clues about how a drug would work to slow down this dread disease:

"A study of the genomes of about 1,800 Icelanders found that the mutation "confers a very, very strong protection against the disease," says Kari Stefansson, a geneticist at deCODE genetics in Reykjavik and one of the study's authors.

People who had the mutation produced about 40 percent less of the proteins that become amyloid beta plaques, Stefansson says.

Previous genetic studies had found only mutations that increased a person's chance of getting Alzheimer's because they increased production of amyloid beta.

"This current mutation actually reduces amyloid beta production," Vassar says, "and it's protective for Alzheimer's disease."

One reason scientists are excited by the discovery is because of the way the mutation works, he says.

In order to form amyloid beta, the brain has to first cut up a larger molecule. It does this using an enzyme called BACE1.

"BACE 1 is like a pair of molecular scissors and what the mutation does is sort of interfere with the way the molecular scissors can cut," Vassar says. "It sort of dulls the blades."

That's exactly what drug companies are trying to do with experimental drugs known as BACE1 inhibitors. Several of these drugs are now being tried in people, although definitive results are probably years off.

If the experimental drugs do work against Alzheimer's, they might also help older people who don't have the disease, Stefansson says.

Ordinarily, people in their 70s, 80s and 90s have a slow but steady decline in memory and thinking, he says. But the Icelandic researchers found that this happened more slowly in people who carried the mutation.

The finding suggests amyloid beta is involved not only in Alzheimer's disease, Stefansson says, but also in the typical memory and thinking problems associated with aging.

The new study also makes it clear that amyloid beta is the key to finding a treatment for Alzheimer's, according to Rudolph Tanzi of Harvard Medical School and Massachusetts General Hospital, a researcher who helped discover the gene studied by the Icelandic team.

Tanzi says Alzheimer's researchers and drug companies need to attack amyloid beta with the same determination that heart disease experts began attacking cholesterol several decades ago.

"We've got to have that same focus with Alzheimer's disease, and I'm hoping that this paper will galvanize us to say, 'OK, this is our target,' " Tanzi says.

Most researchers agree. But some still think amyloid isn't the whole story. They point out that so far, no drug that targets amyloid has managed to slow down Alzheimer's."
- http://www.npr.org/blogs/health/2012...off-alzheimers

[ollinger]

Your last sentence is the key. My reading of the Alzheimer's literature is that some of the zeal about amyloid has started to wane.

[charliefedererer]

There has been some speculation that amyloid is just an innocent bystander of the process, maybe even a reaction by the body to prevent the Alzheimer's from progressing even quicker.


But this new paper seems to add more evidence that amyloid is in fact the problem:

"But what intrigues researchers is how it [the newly disccovered gene mutation] protects the brain. It does the reverse of what the mutations that cause Alzheimer’s do. Those mutations lead to excessive amounts of a normal substance, beta amyloid, in the brain. The protective mutation slows beta amyloid production, so people make much less."

"The protective gene even appears to override a very strong risk factor for Alzheimer’s disease in old age — two copies of a gene known as ApoE4. Ninety percent of people with two ApoE4 genes get Alzheimer’s by age 80. But Dr. Stefansson says there are 25 people in his study with two copies of ApoE4. None have Alzheimer’s disease."

"The discovery of the protective gene mutation provides strong clues. People with the mutation make substantially less beta amyloid, but other than that they are no different from anyone else. And they do not get Alzheimer’s."

"If for no other reason, the discovery’s implication for drug development “is hugely important,” said Dr. David Altshuler, a genomics expert at Harvard Medical School and the Broad Institute of Harvard and M.I.T. who was not involved with the research.

It indicates, he said, that drug companies’ big bets on anti-amyloid treatments could pay off.

“This paper provides strong evidence that it would work in the general population if you did it right,” Dr. Altshuler said.

Dr. Samuel Gandy, an Alzheimer’s researcher who directs the Mount Sinai Center for Cognitive Health, had a similar response, calling the finding “extraordinarily important” — the most significant in the field since researchers first reported a mutation that leads to the disease, 22 years ago."
- http://articles.boston.com/2012-07-1...tation-amyloid


I have to admit when I read the article chills ran up and down my spine.

If there really is evidence that some people in the study with a clear gene mutation for the the development of Alzheimer's did not develop it because of the presence of this second rare mutation that prevents amyloid formation, then hopefully we are on the cusp of a real breakthrough.


Though drugs that mimic the effect of the new gene mutation are already being tested, the possibility arises for gene therapy through cultivating the gene in another vector and tranferring it to early victims of Alzheimer's with a viral delivery system.


Yes, it's too soon for many to be excited, but this really seems to be a step in the right direction, and I for one am already excited.

Perhaps the immortal words of Dr. Warren in the Ether Dome at the first demonstration of anesthesia can even be cited - "Gentlemen, this is no Humbug".

[Talker]

Originally Posted by r2473

Did I go to McDonalds this evening?

I can't remember.

A good excuse to go there twice.

[christo]

A question to you learned gentlemen.
Is Alzheimer's a disease that has always been prevalent amongst seniors and was undiagnosed? is it now overdiagnosed? Is it a result of the toxic environment we live in? And most of all as I work in a Hospital environment and believe the Pharmaceutical industry has killed many more people than it has saved, can drugs truly help?

[ollinger]

1) Alzheimer's is more prevalent as longevity has increased. In the mid 20th century average longevity was about 65 years. It is now a good deal longer, and Alzheimer's is a condition that can begin, most in the field agree, up to about age 80. So it has become more prevalent.
2) There's no good evidence of an environmental cause. The myth about aluminum and aluminum cookware was discredited long ago, as the senile plaques and neurofibrillary tangles seen in brains toxic from aluminum are structurally different from those seen in Alzheimer's.
3) Notwithstanding your somewhat irrational view of pharmacetuticals, the rest of the cogitating world believes the great strides in longevity the past century or so are due to pharmaceuticals, though the bulk of the credit would go to the development of antibiotics, which greatly increased longevity.

[OTMPut]

Most notable "strides in longevity" is actually from prevention - attributed to better personal hygiene, lifestyle, clean environment, etc.
Pharma's contribution is limited but nothing spectacular.

[Soul]

I recall reading Dr. Larry McCleary book on alzheimer's disease and type 3 diabetes. Dr. McCleary is the retired Acting Chief of Neurosurgery at Denver Children’s Hospital. He recently gave an interview on Jimmy Moores show which I thought was interesting.

"‘Diet And The Three A’s: ADHD, Autism and Alzheimer’s’ | Dr. Larry McCleary"

http://livinlavidalowcarb.com/blog/a...mccleary/14064

[ollinger]

OTM
^^ Nonsense. There was a spectacular increase in longevity in the mid 20th century around the time antibiotics were introduced. Children used to routinely die from pneumonia, and things like that suddenly stopped happening with regularity. Hygiene didn't suddenly improve at that time, food additives were increasing, and the environment at that time was getting worse, not better.

[OTMPut]

I am sure you know how many Cholera killed and still kills.

[Bartelby]

Don't know the answer to the prevention versus antibiotics question, but there was a notable increase in the well being of the general population in the fifties and sixties as compared to the thirties and forties.

Poverty, unemployment and poor housing and sanitation were quite common pre-war, but antibiotics are probably the biggest innovation in medicine so its hard to say.

[sureshs]

Originally Posted by christo

A question to you learned gentlemen.
Is Alzheimer's a disease that has always been prevalent amongst seniors and was undiagnosed? is it now overdiagnosed? Is it a result of the toxic environment we live in? And most of all as I work in a Hospital environment and believe the Pharmaceutical industry has killed many more people than it has saved, can drugs truly help?

How did you come up with such a view? It is not rational at all.