BEACoN is an acronym that is short for “Biomarker Exploration in Aging, Cognition, and Neurodegeneration”. This is a collection of related research studies funded by the National Institute on Aging led by Dr. Michael Yassa. There are a number of research studies that are connected to BEACoN. You can read about them here. BEACoN brings together scientists and clinicians from many disciplines to work together on understanding the mechanisms of Alzheimer’s disease so that we may design better therapeutics and preventative strategies.

Biomarkers are measures of what is happening inside the living body, shown by the results of laboratory and imaging tests. Biomarkers can help doctors and scientists diagnose disease and health conditions, find health risks, in a person, monitor responses to treatment, and see how a person’s disease or health condition changes over time. For example, an increased level of cholesterol in the blood is a biomarker for heart-attack risk.

Changes in the brains of people with these disorders may begin many years before memory loss or other symptoms appear. Researchers use biomarkers to help detect these brain changes in people, who may or may not have obvious changes in memory or thinking. Finding these changes early in the disease process helps identify people who are at the greatest risk of Alzheimer’s or another dementia and may help determine which people might benefit most from a particular treatment.

Use of biomarkers in clinical settings, such as a doctor’s office, is limited at present. Some biomarkers may be used to identify or rule out causes of symptoms for some people. Researchers are studying many types of biomarkers that may one day be used more widely in doctor’s offices and other clinical settings.

Source:
Biomarker for Dementia Detection and Research Fact Sheet. NIH, National Institute on Aging. NIH Pub No. 18-AG-8044 . April 2018

There are some tests that will tell you if you have what is known as familial Alzheimer’s disease. However, the most common form of Alzheimer’s disease is known as “sporadic,” meaning that there isn’t just a single gene (or collection of genes) that absolutely determine the development of Alzheimer’s disease. Rather, in the cases of sporadic Alheimer’s disease, the odds of developing the disease might be higher depending on certain risk factors (metabolic syndrome, cardiac disease, sleep apnea, stroke, presence of one or more APOE4 alleles, etc.).

A neuron is the primary cell type of the brain. There are other cell types that act as support for these cells (providing nutrients, helping conduct signals, providing immune support). These cells are composed of several parts: a cell body (think of it as the computer), dendrites (think of these portions as the peripherals [eg. keyboard, mouse, – what is receiving information for the computer]), axon (think of it as the wires of a computer cable), and axon terminals (think of it as the computer screen – what is transmitting the information).

Amyloid plaques are dense, sticky clumps of a protein called beta-amyloid that develop extracellularly – or outside the cell. The enzyme that produces the protein is known as Amyloid Precursor Protein or APP. Normally, there is a small quantity of beta-amyloid protein that is produced, but glia – the brain’s internal clean-up crew cells, will promptly and efficiently break down the proteins before they become large sticky plaques. This does not necessarily mean that the  presence of the beta-amyloid plaques are causing Alzheimer’s disease, or even cognitive impairment. The plaques could be just a symptom of an impaired clean-up system in impaired aging. The plaques could just be relatively benign features on their own.

Tau tangles are dense tangles of a protein called tau that normally acts to stabilize the structure of a neuron intracellularly – or inside the cell. When tau undergoes changes and becomes “hyperphosphorylated”, its structure is compromised, it forms tangles, which then destabilizes microtubules consequently impairing intracellular transport. Think of it as the support beams under highways, when the support is compromised, the highway is compromised. Normal transportation across these systems are compromised as a result, and without critical transportation of information and nutrients the cell will eventually die. In Alzheimer’s disease, one finds these tangles throughout the brain, but most significantly in regions deep in the brain having to do with learning and memory.

At this time being ‘positive’ or ‘negative’ isn’t clinically diagnostic – meaning that knowing your ‘status’ doesn’t actually give you information as to whether you will go on to develop Alzheimer’s disease or even become cognitively impaired. While these two proteins are considered hallmarks of Alzheimer’s disease (meaning that they are always found in the brains of person’s who pass away with AD), scientists also find these proteins in the brains of persons who are, by all rights and reasons, without any cognitive impairment, and in the brains of ‘super-agers’.

Furthermore, part of what we are investigating in this study is whether the deposition of these proteins in space and time offers better prediction of successful vs. impaired aging than a simple binary positive vs. negative result.

As part of this study, we also explore the impact of undergoing biomarker testing on a person’s desire to learn biomarker status and attitudes toward Alzheimer’s disease. We ask our study participants to complete some questionnaires both pre- and post-PET scanning to give us more information on this impact and to better understand the wishes of our participants for knowing the results of their scans.

One Tau PET scan is 740 millirems
One Amyloid PET scan is 903 millirems

The total radiation dose over the course of the entire study period of 2 years from the two amyloid and two tau PET/CT scans is 3286 millirem.  For comparison, persons in the United States receive a radiation dose of about 310 millirems every year from natural sources of radiation, including from the sun, air, water, and soils, so the radiation exposure from PET/CT scans in this study over the entire study is equivalent to about 10 extra years of natural background radiation.

There are no known short-term health effects associated with this amount of radiation exposure.  The primary risk from radiation exposure at this level is the potential for a very small increased risk of future cancer.  If you are especially concerned with radiation exposure, you should discuss this with the study doctor.

A person who is over the age of 90 who is able to consistently perform similar to someone who is 40 years old on neuropsychological assessments for processing speed and memory.

Image source: https://ehonami.blob.core.windows.net/media/2018/09/how-to-get-a-super-ager-brain-to-avoid-dementia-800×600.jpg

The hippocampus is a subcortical region in the brain, meaning that it is a region deep in the brain instead of on the outermost parts. The hippocampus is very important for learning and memory. It doesn’t store memories per-se, but it acts more like an indexer, helping to ‘consolidate’ short term memories into long-term memories in the cortex. The hippocampus is seen to be diminished in size in patients with Alzheimer’s disease, but also in other disorders that affect memory like depression. As part of this study, we measure the size and activity of the hippocampus on the images collected during the MRI procedure.

There is a pronounced shrinkage of the brain in a person with Alzheimer’s disease. This is due to widespread cell loss throughout the brain.

Each questionnaire we give has a specific purpose, like testing working memory, general thinking ability, problem-solving, and many more. The differences between people may be so small, they can only be seen when we compare and analyze a lot of these tests.

Saliva is only part of the picture; it can tell us quite a lot, and we are even testing if saliva is a good measure of brain tau, one of the proteins implicated in Alzheimer’s disease. We ask that participants consider providing both saliva and blood samples, because the type of tests we run on each is different, and have a specific purpose.

No, unfortunately at this time we do not have a treatment for Alzheimer’s disease. There are three drugs on the market right now that do reverse/slow symptoms for six months. However, symptoms usually re-appear (often worse) after this time period. This is usually the time that families use to see their loved ones again and make necessary plans for their future. This why Alzheimer’s disease clinical trials are working hard towards finding an effective treatment.

Changes can include increased forgetfulness, increased agitation, confusion, inability to perform daily activities, inability to engage in hobbies, and trouble understanding situations, explanations, and associations. Alzheimer’s disease is diagnosed using a variety of neuropsychological tests, neuroimaging like MRI, CT and PET, as well as interviewing loved ones about any changes they have seen. As of right now, Alzheimer’s disease can only be definitively diagnosed after death, when physicians review changes in the brain and compare it to tests conducted previously. Our laboratory does not give a diagnosis of Alzheimer’s disease, but we do encourage all participants to see their physician if they are concerned about their risk. If we see something alarming in your testing we will let you know and try to provide you with guidance on next steps.

An IRB stands for an Institutional Review Board, and they are a group of scientists and non-scientists responsible for reviewing every part of a research study involving humans. The IRB’s role is to protect the rights and welfare of human subjects involved in research. The IRB also assures that the research complies with applicable regulations, laws, and institutional policies.