Alzheimer's Disease: New Research in Screening and Treatments

Dr. Roy, a medical scientist studying Alzheimer’s disease at the University of Wisconsin Madison, recently drove down to Chicago to talk about his incredible new research into the exact mechanism of the disease and how researchers might go about actually utilizing this information.  Alzheimer’s disease is a degenerative disease which most often occurs during middle or old age, and up to this point, there has been no easy and cost-effective way to successfully identify this disease and the extent to which it might occur, nor have there been any major breakthroughs in an effective treatment that doesn’t involve the ever-popular “diet and exercise” method.  Alzheimer’s disease is physiologically identifiable post-mortem through an examination of the brain tissue, but is also signaled in living people by the unusually high levels of beta-amyloids in the brain and cerebrospinal fluid.

Dr. Roy’s approach utilizes the popular CRISPR/Cas9 technology, which he is trying to use to modulate this beta-amyloid production.  CRISPR/Cas9 is particularly popular among researchers because of its ability to actually edit DNA and subsequently alter what proteins the genome can produce.  While less than 10% of Alzheimer’s cases are believed to be inherited, this method is still valuable to edit mutations that might have arisen due to natural errors in genome copying and maintenance.  This potential treatment would target an amyloid precursor protein -- a protein that is responsible for generating such large amounts of beta-amyloid fragments -- and aim, in a one-time procedure, to effectively “turn off” the pathway for beta-amyloid creation.  This treatment is a long way off, but seems to be a promising possibility for Alzheimer’s disease in the future.

However, one problem remains: how do we know who actually has Alzheimer’s disease?  In America, 10% of people aged 65 and older are affected by and 32% of people aged 85 and older have the disease.  Currently, there are two ways to test for the disease by measuring the amount of amyloids in a living body: positron emission tomography (PET scans) and lumbar punctures.  PET scans are cost-prohibitive and lumbar punctures come with a host of risks, including infection and paralysis. Neither are realistic for mass screenings, which, with the sheer quantity of the population being affected, would be optimal.  Mass screenings would be an ideal way to determine who needs a treatment if technologies like Dr. Roy’s actually work. An article published by Scientific American details a promising and inexpensive new way to test for these amyloids that are caused by Alzheimer’s.  The researchers studying this thought outside of the box and tried to detect amyloids in a place we don’t currently look for them: the blood.

These researchers, based in Japan, believe enough amyloids making it through the blood-brain barrier to be able to effectively test for them with a simple blood test.  This test, if successful, would not only provide a much cheaper and safer alternative to traditional Alzheimer’s testing, but would even be able to help in distinguishing between Alzheimer’s and other forms of dementia in patients experiencing symptoms.  Their blood test is based on a technique called immunoprecipitation with mass spectrometry, which uses specific antibodies to bind and identify specific proteins. In this case, the protein being bound is the amyloid protein.

Amazingly, this blood test is something that’s already in clinical testing stages.  In a controlled trial setting which included 121 people from Japan and 252 people from Australia and individuals with normal brain function ranging all the way to severely impaired by the disease, it was found that the amount of amyloid present in the blood did, in fact, correlated with the degree of cognitive impairment.  The group conducting the research is currently trying to expand to other parts of the world and reach a larger audience in order to generate a better dataset for the amyloid concentration to Alzheimer’s impairment ratio.

Ultimately, treatments like Dr. Roy’s would be most effective if combined with wide-spread, cost-effective and non-invasive screening measures such as the one being researched by the Japanese group.  While the implementation of either is a long way off, the research being done on them now could help generate new ideas and produce more novel medical technologies.

1 https://www.dshs.texas.gov/alzheimers/qanda.shtm

Stetka, Bret. “A Big Step toward a Blood Test for Alzheimer's.” Scientific American, 31 Jan. 2018, www.scientificamerican.com/article/a-big-step-toward-a-blood-test-for-alzheimers/.

The physical approximation of APP and BACE-1: A key event in Alzheimer's disease pathogenesis. Jichao Sun and Subhojit Roy*

Developmental Neurobiology 2017 Nov 6. doi: 10.1002/dneu.22556.