from the I've-forgotten-what-I-was-going-to-write dept.
A study from researchers at Massachusetts General Hospital (MGH) and Brigham and Women's Hospital (BWH) reveals for the first time exactly how mutations associated with the most common form of inherited Alzheimer's disease produce the disorder's devastating effects. Appearing in the March 4 issue of Neuron, the paper upends conventional thinking about the effects of Alzheimer's-associated mutations in the presenilin genes and provides an explanation for the failure of drugs designed to block presenilin activity.
[...]
"Our study provides new insights into Alzheimer's disease by showing how human mutations that cause the disease lead to neurodegeneration and dementia," says Raymond J. Kelleher III, MD, PhD, of the MGH Department of Neurology and Center for Human Genetic Research, co-senior author of the Neuron paper. "We found that mutations in the presenilin-1 gene promote the hallmark features of the disease by decreasing, rather than increasing, function of the presenilin-1 protein and the gamma-secretase enzyme. In addition to the important therapeutic implications of our findings, we have also generated the first animal model in which an Alzheimer's-disease-causing mutation produces neurodegeneration in the cerebral cortex."
(Score: 5, Insightful) by bzipitidoo on Thursday March 05 2015, @03:31PM
Genes again, is it? A study on the inherited form of Alzheimer's?
What about all the other causes of Alzheimer's? For instance, reckless profiteering by Big Pharma. Specifically, Hormone Replacement Therapy for older women was a big fad for a while in the late 90s and early 2000s. "In May 2003, researchers reported that women who had been taking estrogen combined with progestin experienced twice the risk of developing dementia as women taking a placebo" ( http://www.alz.org/dsw/documents/hrt.pdf [alz.org] ) My mother was treated with HRT in the late 1990s. I noticed a personality change starting at that time, and thought only that she'd resolved to turn over a new leaf. Now I think that was the start of her mental decline. In 2009 she was diagnosed with Alzheimer's, and today she can't remember her own name. We took her car keys away in March 2010, after too many suspicious paint marks on the bumpers that she had no idea were there. In Oct 2013, she became incontinent.
Pollution could play a role too. There's this idea that the mercury in dental fillings could produce dementia like symptoms over a long period of time. The literature on this point is confused, some saying there is no connection, and others saying there is.
There's also the notorious notion that cell phone radiation could have an effect. We don't really know, because, again, powerful interests have managed to suppress scientific inquiry into that question.
It's hard enough doing a good study to find out for sure on such questions. Whether mercury causes Alz or makes it worse is hard to say, but I do know that mercury is one of the toxic heavy metals that should be avoided, period. All the time. we're advised not to eat fish, because of mercury. But we have powerful interests routinely running propaganda campaigns disguised as science. We've seen this in denial of Climate Change sponsored by Big Oil, denial of safety issues with Bisphenol A and other plastics sponsored by plastics trade groups, inadequate softball tests that incorrectly showed that the lead in the brass used for faucets does not leech out, created by the plumbing industry, and of course the granddaddy of them all, Big Tobacco's campaign to deny that nicotine is addictive. I'd like to ask, can we stop this kind of foolishness? These industries have no respect or appreciation for honesty. When they won't dare try propaganda, when marketing understands that some manipulation is unacceptable and won't do it not just out of fear, but also because they themselves appreciate facts and honesty, then we can again mostly trust our sciences.
For years now, genes has been the go to reason for any and every medical condition. It's a huge cop out. No external factor is to blame, you're just unlucky. Your parents gave you bad genes, so sorry. And, even if it is genes, there's such a thing as whether they are expressed, and what causes them to be expressed or not. And one of the things that causes or suppresses gene expression? Chemicals in the environment.
(Score: 0) by Anonymous Coward on Thursday March 05 2015, @05:02PM
I'm sure you can blame much of it on genes. Just like you're more vulnerable to cobra venom since you don't have the genes of a mongoose or cobra: http://www.nytimes.com/2010/10/26/science/26creatures.html [nytimes.com] ;)
So lots of people might be immune to some stuff while a few others might be vulnerable.
(Score: 0) by Anonymous Coward on Thursday March 05 2015, @06:31PM
This is looking a gift horse in the mouth.
So some small group of scientists have a finding, and they should have shut the f up until they solved every possible cause of Alzheimer's, including retroactively your mother's?
I can't see that working. Complex things are complex.
Sorry about your mother, Alzheimer's sucks.
(Score: 3, Funny) by DeathMonkey on Thursday March 05 2015, @06:51PM
Study is totally useless! This genetic study of Alzheimers doesn't even prove that black holes exist.
(Score: 0) by Anonymous Coward on Thursday March 05 2015, @07:33PM
Genetic causes and predispositions is a great place to start to understand disease.
How do you control for a large number of environmental factors? How do you perform experiments to assess their individual contributing role? How do you fix the disease after the fact?
Genes help you narrow down a pathway. Inhibitors of gamma secretase have already failed in clinical trials and this study may give some insight into why that happened. This is progress.
(Score: 4, Interesting) by gringer on Thursday March 05 2015, @08:04PM
You're basically complaining that someone has found a repeatable series of instructions that can be carried out to demonstrate a particular flaw in how our body works, and we should be instead concentrating on finding the non-repeatable things — "That's not a bug, this is a bug."
If you were saying the same thing about a bug in a computer program, you'd be blasted for it. Just because someone has found a causative variant for a particular type of Alzheimers, it doesn't mean people can't keep looking for other causes. Knowing that defects in a particular gene lead to Alzheimers is a good thing, and can help remarkably in finding out ways to deal with the disease. Once you find the cause of a bug, you're 90% of the way to fixing it.
Ask me about Sequencing DNA in front of Linus Torvalds [youtube.com]
(Score: 2) by bzipitidoo on Friday March 06 2015, @04:26AM
From the article: "While inherited or familial Alzheimer's disease (FAD) is very rare, accounting for only around 1 percent of cases" It's good to have progress, and I certainly hope this is relevant to the other 99% of Alzheimer's cases. And unlike studies on mice, there is no question about whether this is another case where mice are not similar enough to people for the results to be applicable. I also understand that in a way we're lucky there are some cases that lack an environmental cause, as the remaining possible causes are therefore easier to isolate. Yes, very worthwhile study.
But I'm complaining about the very thing that lead to "bug" becoming the euphemism for a flaw in a program. It's no-fault science. I'm not looking for scapegoats, but we've gone too far the other way, and won't even look at causes that could implicate someone or something. It's highly selective science. Instead of cherry picking the results, we're cherry picking the experiments. Experiments that might show problems that could hurt some established business are routinely squelched. I fear this Alzheimer's study is a product of that very sin, looking only at cases that can be blamed squarely on genetics, even though such cases are only 1% of all cases. What would you say, if we could have known all about the causes and cures of Alz 20 years ago, if only we'd been allowed to pursue the most promising directions of study? If you think that's impossible, think of AIDS. Think also of how long it took to remove lead. We've known lead is toxic since the days of the Roman empire, yet in recent times it was added to gasoline, paint, and the brass of faucets for drinking water. Concerns that lead could leech out were brushed aside. Leaded paint was used not only in homes, but even on drinking glasses that fast food restaurants once gave out to children. Figurines for D&D were made of 100% lead. Lead has been used for sinkers for fishing, and bullets. While things have improved, lead is still being used today, sneaked into places where manufacturers hope no one notices or if they do, won't care. Incredible. So, yes, a good study, but are there other studies that should be done but aren't, for political reasons?
Thanks to football, we now understand that frequent brain trauma can cause Alzheimer's as well as many other mental problems. I already mentioned Hormone Replacement Therapy and cell phone radiation. Another big factor is diet. Perhaps too much sugar or not enough spice leads to Alz.
(Score: 2) by gringer on Friday March 06 2015, @09:57AM
What would you say, if we could have known all about the causes and cures of Alz 20 years ago, if only we'd been allowed to pursue the most promising directions of study?
I would be astonished that we knew the precise direction to take with no dissapointing results. Research is hard, and frequently "the most promising directions of study" are only known in hindsight. The world just has a tendency to not work in the ways that we expect.
Lead is actually a good example of this. It's a very useful metal — fairly common, very colourful, malleable, heavy, and has a low melting temperature. It's not too surprising that people want to use it for everything. Sure, okay, so lead is poisonous when consumed in large quantities, but if it's solid, there's no way that it can get into anything liquid. Okay, so it makes water poisonous when we leave a lead vessel filled, but pipes always have running water, so there's not enough time for a substantial amount of lead to get into that. Right, so making things out of lead is a bad idea, but surely combining it with another element will make that less of an issue. Hmm... it seems to leech into the air when ground and heated, but what about paint? That's a thick thing that stays around for centuries. Nope, that has atmospheric problems as well, but if it's nicely sealed in a car engine, it should be perfectly fine. Okay, that caused problems as well, but look how much power it can store when combined with sulphuric acid! We can seal it up really well inside a thick plastic container, and there's no way any of that lead can get out....
It's surprising how bad lead is, but not surprising that it's still used despite its danger.
Ask me about Sequencing DNA in front of Linus Torvalds [youtube.com]
(Score: 0) by Anonymous Coward on Saturday March 07 2015, @05:32PM
ignore these establishment whores. these people think defending industry controlled science and research proves how modern and sophisticated they are. These are the same people that try and label anyone who questions the safety and/or efficacy of vaccines(as currently available to the masses in the US) as ignorant, dangerous cultists(some may be, but that's not the point) while letting the real disease at the US federal governament(FDA, CDC, etc) and big agri+pharma mislead and damage a whole nation/world. Or like people that dare question whether "climate scientists" might be prostituting themselves for grants from NWO politicians who want to tax people for breathing the governments' air while they spray unknown chemicals out of jet engines while discussing whether they should "start" geoengineering experiments. These modern sophisticants, who are so brainwashed they can't look into the sky and remember that contrails didn't used to turn into complete cloud cover right before the eyes.
While these specific researchers probably had the best of intentions they are compartmentalized and controlled as a whole. As you've pointed out, the overall research rarely looks into the root cause. They should be looking for the root cause and prevention, while also looking for safe hacks for those already affected. The medical establishment never looks at their own practices nor their co-conspiritors at the big corps(the ones poisoning everyone, every day). They look for "treatment" targets and gather intel on the "human" body for various untrustworthy financiers.
the US medical establishment is a embarassment and a menace and anyone who defends them is complicit.
(Score: 0) by Anonymous Coward on Thursday March 05 2015, @08:24PM
You remind me of a guy I work with, who explains that - in his considered opinion (Bachelor of Arts in Politics and Economics) - spaceflight is a complete waste of time and money until we've solved every other problem on Earth.