Alberto J. Espay, MD, MSc, FAAN Professor of Neurology Director and Endowed Chair Gardner Family Center for Parkinson's disease and Movement Disorders University of Cincinnati Academic Health Center

11 Dec Novel Alzheimer’s Finding: Increasing Levels of Normal Protein, Aβ42 May Be Linked to Improvement

Posted at 20:40h in Alzheimer's - Dementia, Author Interviews, Biomarkers by

MedicalResearch.com Interview with:

Alberto J. Espay, MD, MSc, FAANProfessor of Neurology Director and Endowed Chair Gardner Family Center for Parkinson's disease and Movement Disorders University of Cincinnati Academic Health Center

Prof. Espay

Alberto J. Espay, MD, MSc, FAAN
Professor of Neurology
Director and Endowed Chair
Gardner Family Center for Parkinson’s disease and Movement Disorders
University of Cincinnati Academic Health Center

MedicalResearch.com: What is the background for this study? What are the main findings

Response:  Because aducanumab, lecanemab, and donanemab were only in a minority of anti-amyloid treatments showing a benefit, I was interested in finding out what makes them special. It turns out that they not only clean the brain from amyloid, like other monoclonal anti-Aβ antibodies, but they also increase Aβ42 in the spinal fluid, which is a measure of the normal protein in the brain. Everyone with Alzheimer’s has low Aβ42 levels because this protein clumps into amyloid plaques.

I tested the hypothesis that increasing Aβ42 could explain the cognitive outcomes at least as well as decreasing amyloid, and that’s exactly what we found. This suggests that restoring the normal protein levels, Aβ42, may explain why some anti-amyloid treatments (presumably those that increased those levels the most) come with benefits.

MedicalResearch.com: What should readers take away from your report?

Response: That cleaning the brain from amyloid plaques may not (at least alone) explain the potential benefit of the newly approved monoclonal antibodies for Alzheimer’s disease, since many other anti-amyloid treatments have accomplished that. The alternative explanation for any benefit is that they increase the levels of the normal protein, Aβ42. 

MedicalResearch.com: What recommendations do you have for future research as a results of this study?

Response: That all research include measures of both ends of the protein story, the normal protein, Aβ42, and the abnormal aggregated version of it, amyloid plaques. When only one side is reported, the conclusions may be incomplete at best, misleading at best.

MedicalResearch.com: Is there anything else you would like to add??

Response: We need to start looking at Alzheimer’s as problem of loss neurons and proteins, including Aβ42, rather than as a gain of anything, such as amyloid. At the end, any “accumulation” of amyloid does not translate into brain swelling. The brain continues to shrink –remarkably faster with the anti-amyloid monoclonal antibodies.

Any disclosures?  My key disclosure is that I am co-developer of a patent for protein replacement and cofounded a company, Regain Therapeutics, to conduct the animal studies to determine future translatability to humans.

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Last Updated on December 11, 2024 by Marie Benz MD FAAD

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