In Search of Disease-Modifying Treatment for Alzheimer’s (Podcast)

An update on biomarkers and various therapies in development

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Disease-modifying treatment for Alzheimer’s disease is not yet available in the U.S. However, most of the approximately 120 pharmaceutical agents currently in clinical trials for Alzheimer’s are focused on changing the biology of the disease.

With targets varying from amyloid pathology to inflammation, test drugs may soon change the outlook for patients.

The newest episode of Cleveland Clinic’s Neuro Pathways podcast explores evolving therapies being studied for Alzheimer’s and other issues in management of the disease. Babak Tousi, MD, head of the clinical trials program at Cleveland Clinic Lou Ruvo Center for Brain Health, discusses:

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  • The current status of Alzheimer’s drug development, including immunotherapies and vaccines
  • Biomarkers to aid early diagnosis
  • Potential preventive therapy
  • The need for precision medicine in Alzheimer’s disease

Click the podcast player above to listen to the episode now, or read on for a short edited excerpt. Check out more Neuro Pathways episodes at or wherever you get your podcasts.

Excerpt from the podcast

Dr. Tousi: Currently, Alzheimer’s biomarkers are based on some types of imaging, like PET imaging, or assessment of cerebrospinal fluid through  lumbar puncture. But we are always looking for other biomarkers, like a simple blood test, which would be more affordable. The aim is to be able to easily repeat such tests a few times and track the progress of the disease or the treatment that we use. This may have seemed impossible a few years ago, but I will not be surprised if we are using blood biomarkers — a blood test for the diagnosis of Alzheimer’s disease — in our practice within a year or so.

One such biomarker, the plasma amyloid beta 42/40 ratio, can help us define who is most likely to have amyloid plaque or develop amyloid plaque down the road. So it’s a good indicator for amyloid pathology.

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Another biomarker that has gotten a lot of attention in the last year is p-tau217, a very promising indicator for amyloid pathology and also tau pathology. It is highly accurate and discriminative between patients with tau-positive and tau-negative PET scans, as well as between those with amyloid-positive and amyloid-negative PET scans. It appears to correlate quite well with the clinical diagnosis of Alzheimer’s disease versus other types of dementia, so it is very likely we will hear more about p-tau217 in the future.

A third biomarker of interest is not indicative of Alzheimer’s disease necessarily. Neurofilament light, or NfL, is indicative of axonal injury neurodegeneration that we’ve seen in other neurological disorders and even in aging, but it has potential to inform the prognosis for patients in terms of how much damage has been done at the axonal level.