Beta-amyloid’s Key Role in Alzheimer’s Toxic Clumps and Need for Personalized Medicine Focus of Talk

Increasing evidence places beta-amyloid aggregates at the center of the toxic protein clumps and neuroinflammation that drive Alzheimer’s, two experts in this disease said, and a personalized, combination treatment likely will be the best way of helping patients.

These insights were shared at a recent Key Opinion Leader luncheon meeting, hosted by AC Immune in New York, that focused on the protein aggregates associated with Alzheimer’s and other neurodegenerative diseases, and possible future therapies or therapy approaches.

Presentations given included those by Michael Weiner, MD, a professor of Radiology and Biomedical Imaging, Medicine, Psychiatry, and Neurology at University of California San Francisco School of Medicine and John Trojanowski, MD, a professor of Geriatric Medicine and Gerontology at the Perelman School of Medicine, University of Pennsylvania.

Weiner, an expert in brain imaging and biomarkers to diagnose and monitor treatment response in neurodegenerative diseases, reviewed what is known about the role of beta-amyloid aggregates in the brain, which are — with  tau protein tangles — a hallmark of  Alzheimer’s disease.

He said that increasing data support beta-amyloid aggregates as the most toxic aggregates in Alzheimer’s, and that their presence induces several events likely involved in the formation of tau protein clumps and neuroinflammation.

Weiner emphasized that potential therapies against tau proteins currently in development and in clinical trials — which include vaccines, antibodies, and small molecules — hold promise in treating Alzheimer’s and other neurodegenerative diseases.

He also highlighted the importance of early diagnosis in Alzheimer’s disease, and reviewed the latest advances in brain positron-emission tomography (PET) imaging, and blood and brain fluid biomarkers.

“Alzheimer’s disease can be thought of as an amyloid induced tauopathy [disease associated with toxic clumps of tau], and therefore therapeutics targeting amyloid and tau hold much promise in finding a cure for this devastating disease,” Weiner said in a press release.

“Imaging and biomarker diagnostics, particularly blood tests, will facilitate early treatment and improved clinical outcomes,” he added.

Trojanowski, who was involved in the discovery of key proteins involved in several neurodegenerative diseases — including Alzheimer’s and Parkinson’s — highlighted that clumps not only of beta-amyloid and tau, but also of alpha-synuclein and TDP-43 proteins co-exist in varying degrees in a wide range of neurodegenerative disorders, and may work together to increase disease severity.

This suggests that personalized medicine may be the future of treating neurodegenerative diseases, as each disease — or patient — may require a combination of therapies that target several disease-associated proteins, rather than a single therapy targeting a major toxic protein.

“The high prevalence of co-pathologies [co-existence of distinct toxic events] in neurodegenerative diseases, as well variation between individuals, indicates that diagnostics and combination therapy may be the ultimate requirement,” Trojanowski said.

“We’re starting to see a clearer and more important need for precision medicine with the prevalence of co-pathology in AD [Alzheimer’s disease], Parkinson’s and other neurodegenerative diseases,” Andrea Pfeifer, AC Immune’s CEO, added. “Our current therapeutic and diagnostic pipeline forms the basis of our forward strategy to become a leader in precision medicine as applied to AD and other neurodegenerative diseases.”

Currently, AC Immune has nine products in various stages of clinical development and several potential therapeutic compounds in preclinical studies addressing key targets in these diseases.

A replay of the meeting is available on AC Immune’s website.