The Brain Plaques and Tangles That Cause Alzheimer’s

The Brain Plaques and Tangles That Cause Alzheimer’s

Meryl Comer: The mainstream research has been focused on beta amyloid.  Tau has always been there, but now there is a big controversy about where the progression comes, where does it really lie?  Take that debate on Dr. Gandy. 

Dr. Gandy:  Well certainly people with Alzheimer’s disease have two sorts of lesions in their brains, two sorts of clumps of protein.  Some of these clumps are in between nerve cells, and others are inside nerve cells.  The ones that are in between the nerve cells are called amyloid plaques.  The clumps that are inside the nerve cells, which are twisted, are called tangles or neurofibrillary tangles.  Now for many years we didn’t sort of know what the sequence of events was, but it is very clear now that all the genes that cause Alzheimer’s disease point to the buildup of amyloid. So it appears that Alzheimer’s disease amyloid comes first and tangles come next.  They may be extremely important in understanding why the nerve cell dies.  Now the disease that Dr. Troncoso mentioned, frontal temporal dementia, has also helped us to understand the relationship between plaques and tangles because in that disease the mutations that cause the genetic forms are in the protein called tau that builds up and causes tangles.  People with frontal temporal dementia get tangles, but they never get plaques, so in Alzheimer’s disease plagues can cause tangles, but in frontal temporal dementia tangles don’t cause plaques.

Meryl Comer: Well why is it so hard these days to get a grant from NIA around beta amyloid when you can get it for tau?

Dr. Gandy:  Well so there is a specific reason for that that’s really evolved a lot in the last year.  There is a study that was reported this spring that showed using an antibody, a chemical aimed at the amyloid substance... that if people with mild Alzheimer’s disease received antibody infusions, anti-amyloid infusions, for a year and a half that the amyloid buildup in their brains would go down by about 25%.  They didn’t change at all clinically.  They didn’t get any better in terms of their cognitive function.  Why is that? Because we didn’t start early enough, because we didn’t treat long enough or because it’s actually another form of amyloid, not the plaques, but these floating clumps called oligomers?

Meryl Comer:  You wanted to make a point, yes, doctor. 

Dr. Troncoso:  Yeah well, I think that there is a lot of debate between the amyloid and tau deposition, but I think one should not get stopped at that point of that argument because it’s perfectly possible that one of these abnormalities, let’s say amyloid may trigger the rest and there is more than amyloid and tau.  We haven’t spoken, but there is a very significant inflammatory, inflammation in the brain that once you have perhaps amyloid and tau trigger that event it becomes self-sufficient.  It actually may even promote more amyloid or more tau deposition, so I think that tau it may be as important as amyloid, but it may be later on in this progression of the disease. And if you could actually target each of these elements it probably would be beneficial. So I don’t see really a tremendous dichotomy, antagonism between looking at amyloid and tau.  I think that both are perfectly legitimate targets of research and one more perhaps disgression in terms of the dementia that is being seen in patients who have head trauma.  Most of that, the lesions that they have is of the tau type, so I think both of these targets amyloid and tau should be addressed.  There is no reason to eliminate one of them.

Dr. Gandy:  There is the one experiment to mention that might also explain why the shift sort of toward tau.  A lot of what we’ve learned about Alzheimer’s disease is from mouse models.  Mice normally never ever get Alzheimer’s disease because their amyloid is different enough that it doesn’t clump and build up.  If we then put into a mouse the gene for amyloid and with a mutation that would cause it to build up and the gene for tau so that it will get tangles, then as that animal ages it will get buildup of plaques and tangles just like, similar to humans with Alzheimer’s disease.  They will then lose their ability to find their way around their cage or to find their way around a swim maze.  If you then treat them with a drug or substance that will decrease the levels of tau, will lower the tau down, the cognitive function comes back, so it’s possible to sort of render the amyloid inert if you can turn down the tau at least in the mouse model.

Amyloid plaques and neurofibrillary tangles inside the brain are the best explanation we have for how Alzheimer’s develops.

LinkedIn meets Tinder in this mindful networking app

Swipe right to make the connections that could change your career.

Getty Images
Sponsored
Swipe right. Match. Meet over coffee or set up a call.

No, we aren't talking about Tinder. Introducing Shapr, a free app that helps people with synergistic professional goals and skill sets easily meet and collaborate.

Keep reading Show less

4 reasons Martin Luther King, Jr. fought for universal basic income

In his final years, Martin Luther King, Jr. become increasingly focused on the problem of poverty in America.

(Photo by J. Wilds/Keystone/Getty Images)
Politics & Current Affairs
  • Despite being widely known for his leadership role in the American civil rights movement, Martin Luther King, Jr. also played a central role in organizing the Poor People's Campaign of 1968.
  • The campaign was one of the first to demand a guaranteed income for all poor families in America.
  • Today, the idea of a universal basic income is increasingly popular, and King's arguments in support of the policy still make a good case some 50 years later.
Keep reading Show less

Why avoiding logical fallacies is an everyday superpower

10 of the most sandbagging, red-herring, and effective logical fallacies.

Photo credit: Miguel Henriques on Unsplash
Personal Growth
  • Many an otherwise-worthwhile argument has been derailed by logical fallacies.
  • Sometimes these fallacies are deliberate tricks, and sometimes just bad reasoning.
  • Avoiding these traps makes disgreeing so much better.
Keep reading Show less

Why I wear my life on my skin

For Damien Echols, tattoos are part of his existential armor.

Videos
  • In prison Damien Echols was known by his number SK931, not his name, and had his hair sheared off. Stripped of his identity, the only thing he had left was his skin.
  • This is why he began tattooing things that are meaningful to him — to carry a "suit of armor" made up the images of the people and objects that have significance to him, from his friends to talismans.
  • Echols believes that all places are imbued with divinity: "If you interact with New York City as if there's an intelligence behind... then it will behave towards you the same way."
Keep reading Show less