Washington, D.C., Nov. 3, 2021 — As November marks Alzheimer’s Awareness Month, a new review in the American Journal of Psychiatry examines the current state of research on Alzheimer’s disease and potential future directions. Central to the authors’ argument is the unconventional idea that the presence of amyloid and tau are merely biomarkers of the disease, and that treatments focused on them may not improve patient outcomes.

Alzheimer’s disease is a neuropsychiatric disorder affecting more than six million Americans. One in three seniors dies with Alzheimer’s or another dementia according to the Alzheimer’s Association. In “Amyloid and Tau in Alzheimer’s Disease: Biomarkers or Molecular Targets for Therapy? Are We Shooting the Messenger?” the authors, led by Anand Kumar, M.D., M.H.A., review the clinical and neuropathological origins of Alzheimer’s disease and trace the evolution of modern biomarkers from their historical roots.

Since the early identification of the disorder, researchers have looked to neuritic plaques and neurofibrillary tangles as critical to the disease process. Technological innovations such as neuroimaging and biochemical assays have been used to measure biomarkers of Alzheimer’s disease. Over the past two decades, the authors explain, Alzheimer’s treatments have “largely focused on preventing the accumulation of and/or removing” amyloid, and more recently, tau. “Results have been disappointing,” Kumar and colleagues note.

The authors describe a contrarian opinion in the field Alzheimer’s disease that “cell death, and not the presence of Aβ and tau, is the critical pathophysiological event.” In this framework, the “hallmark neuropathology — plaques and tangles — may be ‘defensive mechanisms or damage response protein,’ and therefore targeting them experimentally is a misleading and potentially dangerous approach to AD therapeutics,” according to the authors. They also suggest that alternative approaches, “including the repurposing of older, off-patent drugs, are receiving renewed attention with the growing appreciation that classical biomarkers may not be suitable targets for drug development.”

While there are still many uncertainties surrounding Alzheimer’s disease, today “there is a better appreciation of the complexity of the disorder and the need for further research, especially in identifying other critical pathways and molecules that may serve as more effective therapeutic targets in this devastating disorder,” the authors note. “We may also have reached a critical scientific fork in the road where important distinctions may need to be made between a valid biomarker and a molecular target for drug development,” they conclude.

The study authors include Anand Kumar, M.D., M.H.A., Charles B. Nemeroff, M.D., Ph.D., Joseph J. Cooper, M.D., Alik Widge, M.D., Ph.D., Carolyn Rodriguez, M.D., Ph.D., Linda Carpenter, M.D., and William M. McDonald, M.D.

American Psychiatric Association

The American Psychiatric Association, founded in 1844, is the oldest medical association in the country. The APA is also the largest psychiatric association in the world with 37,400 physician members specializing in the diagnosis, treatment, prevention and research of mental illnesses. APA’s vision is to ensure access to quality psychiatric diagnosis and treatment. For more information, please visit www.psychiatry.org.