Alzheimer’s May Be More Complicated

According to a 2018 annual report released by the Alzheimer’s Association, there are currently 5.7 million Americans living with Alzheimer’s disease. As this number is projected to increase in the next decades, researchers from the University of Texas at San Antonio have come up with a unique approach to studying the disease in hopes of finding therapies that can slow its progression.

TRANSCRIPT

According to a 2018 annual report released by the Alzheimer's Association, there are currently 5.7 million Americans living with Alzheimer's disease.

As this number is projected to increase in the next decades, researchers from the University of Texas at San Antonio have come up with a unique approach to studying the disease in hopes of finding therapies that can slow its progression.

Oftentimes, the terms Alzheimer's disease and dementia are used interchangeably.

In reality, though, there are many different forms of dementia.

Alzheimer's disease is the number-one cause of dementia worldwide.

There are millions of cases, and throughout the years, as deaths from other diseases, such as heart disease, have gone down, Alzheimer's disease deaths just continue to rise.

So, there is a really, really big problem with a lack of available therapies or available drug targets to not cure the disease, but stop its progression.

The problem with there being no cure is that there is a lack of understanding of how the disease operates.

If you're doing diabetes, you know it's insulin you got to worry about.

With Alzheimer's, the only thing they know right now is to worry about senile plaque.

So the goal of this research is to try and find out, what are the molecular players in Alzheimer's, and how do the molecules, the molecular constituents of the brain and the body, change as people progress through the various stages of Alzheimer's?

And, hopefully, if we can understand the biomolecular processes involved in Alzheimer's, we can figure out an interventional method.

Billions of dollars have been spent over the last years trying to better understand the disease pathology.

As of right now, not much is known, and because of that, there's no real way to start developing any potential drug therapy, or really even understand the biomarkers of the disease.

So, basically, what this is, is this is an actual piece of brain from an Alzheimer's-disease patient.

This has been formalin-fixed and paraffin-embedded.

This is a really, really good type of tissue for histology and pathology because it has an infinite lifetime.

Years down the road, you can go back, stain it, look at it under a microscope, and basically look at the different hallmarks in there.

So, there are ways of looking at things like senile plaques and tau with microscopy with this type of tissue What we do with the imagining mass spectrometry is actually cut this tissue onto glass slides, and, with our instrument, we are able to take the tissue, basically raster it with a laser across the tissue, and then localize all of the different components so that you get a really good picture of where on the tissue each thing is localized, and which things are localized in the same area and so on and so forth.

So, senile plaques are some sticky aggregates of what most people consider was nothing but amyloid beta.

And that's one of the reasons we wanted to start, because we know what amyloid beta looks like in our mass-spec.

So, once we figured out the preparation method for amyloid beta -- and being able to do it in a mass spectrometer we're able to actually see the amyloid beta.

And then, to our surprise, we're able to see a whole host of other proteins and peptides that have various known functions in the body, and that are unusual to have been found in the brain.

The optimal thing would be to follow patients, which is unrealistic for us.

But as long as we can use these samples that we have from humans and start to see, 'Okay, what is exaggerated?

What is expressed differently between these healthy brains and these diseased brains?'

We can start to maybe get a new focus.

We feel that, once researches know what the molecular players are, what the proteins and peptides are that are involved in this disease, they will be able to figure out ways of stopping the progression of this disease before it gets to its ultimate end, where the person has the dementia.

Our research here at UTSA has the ability to shed new light on the molecular targets and molecular mechanisms that are at play in the onset and progression of Alzheimer's disease.

And hopefully we have been able to develop a new molecular foci for disease research that will eventually lead to available disease therapies or drug targets.