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Alzheimer’s Signs Reversed in Mouse Study

Alzheimer’s Signs Reversed in Mouse Study

Researchers have successfully reversed the formation of amyloid plaques in the brains of mice with Alzheimer’s disease, thereby improving the animals’ cognitive function.

Investigators from the Cleveland Clinic Lerner Research Institute discovered that gradually depleting an enzyme called BACE1 eliminates the plaques.

The study, which appears in the Journal of Experimental Medicine, raises hopes that drugs targeting this enzyme will be able to successfully treat Alzheimer’s disease in humans. The vast majority of experimental treatments using a rodent model — whether for diabetes or cancer or Alzheimer’s — fail to work in humans.

Researchers explain that one of the earliest events in Alzheimer’s disease is an abnormal buildup of beta-amyloid peptide, which can form large, amyloid plaques in the brain and disrupt the function of neuronal synapses.

Also known as beta-secretase, BACE1 helps produce beta-amyloid peptide by cleaving amyloid precursor protein (APP). Drugs that inhibit BACE1 are therefore being developed as potential Alzheimer’s disease treatments. However, the drugs may have serious side-effects because BACE1 controls many important processes.

Mice completely lacking BACE1 suffer severe neurodevelopmental defects. To investigate whether inhibiting BACE1 in adults might be less harmful, researcher Dr. Riqiang Yan and colleagues generated mice that gradually lose this enzyme as they grow older. These mice developed normally and appeared to remain perfectly healthy over time.

The researchers then bred these rodents with mice that start to develop amyloid plaques and Alzheimer’s disease when they are 75 days old. The resulting offspring also formed plaques at this age, even though their BACE1 levels were approximately 50 percent lower than normal.

Remarkably, however, the plaques began to disappear as the mice continued to age and lose BACE1 activity, until, at 10 months old, the mice had no plaques in their brains at all.

“To our knowledge, this is the first observation of such a dramatic reversal of amyloid deposition in any study of Alzheimer’s disease mouse models,” Yan said.

Decreasing BACE1 activity also resulted in lower beta-amyloid peptide levels and reversed other hallmarks of Alzheimer’s disease, such as the activation of microglial cells and the formation of abnormal neuronal processes.

Loss of BACE1 also improved the learning and memory of mice with Alzheimer’s disease. However, when the researchers made electrophysiological recordings of neurons from these animals, they found that depletion of BACE1 only partially restored synaptic function, suggesting that BACE1 may be required for optimal synaptic activity and cognition.

“Our study provides genetic evidence that preformed amyloid deposition can be completely reversed after sequential and increased deletion of BACE1 in the adult,” Yan said.

“Our data show that BACE1 inhibitors have the potential to treat Alzheimer’s disease patients without unwanted toxicity. Future studies should develop strategies to minimize the synaptic impairments arising from significant inhibition of BACE1 to achieve maximal and optimal benefits for Alzheimer’s patients.”

Source: Rockefeller University Press/Science Daily

Alzheimer’s Signs Reversed in Mouse Study

Rick Nauert PhD

Rick Nauert, PhDDr. Rick Nauert has over 25 years experience in clinical, administrative and academic healthcare. He is currently an associate professor for Rocky Mountain University of Health Professionals doctoral program in health promotion and wellness. Dr. Nauert began his career as a clinical physical therapist and served as a regional manager for a publicly traded multidisciplinary rehabilitation agency for 12 years. He has masters degrees in health-fitness management and healthcare administration and a doctoral degree from The University of Texas at Austin focused on health care informatics, health administration, health education and health policy. His research efforts included the area of telehealth with a specialty in disease management.

APA Reference
Nauert PhD, R. (2018). Alzheimer’s Signs Reversed in Mouse Study. Psych Central. Retrieved on July 16, 2018, from https://psychcentral.com/news/2018/02/19/alzheimers-signs-reversed-in-mouse-study/132747.html

 

Scientifically Reviewed
Last updated: 19 Feb 2018
Last reviewed: By John M. Grohol, Psy.D. on 19 Feb 2018
Published on PsychCentral.com. All rights reserved.