Alzheimer's-associated enzyme can disrupt neural activity in the brain

Neuronal sodium-channel dysfunction is known to cause seizures in both mice and humans. In a supplement to the current paper the investigators present evidence that sodium channel metabolism is altered in the brains of Alzheimer’s patients compared with non-demented individuals of similar age.

“Our study suggests that the BACE inhibitors currently being developed to reduce amyloid-beta generation in Alzheimer’s disease patients may also help prevent seizures by alleviating disrupted neural activity,” Kovacs explains. “However, complete inhibition of BACE activity could interfere with the enzyme’s normal regulation of sodium channels, so therapeutic strategies using those inhibitors will need to be carefully designed.” Kovacs is an associate professor of Neurology at Harvard Medical School.

The Kovacs team hopes to continue investigating how BACE-induced changes in sodium channel metabolism contribute to other Alzheimer’s symptoms and to additional neuronal cell activity. Co-first authors of the Nature Cell Biology paper are Doo Yeon Kim, PhD, and Bryce Carey, of MGH-MIND. Additional co-authors are Laura Ingano, Mary Wertz, and Warren Pettingell, MGH-MIND; Haibin Wang, MD, PhD, Alexander Binshtok, PhD, and Clifford Woolf, PhD, MGH Anesthesia-Critical Care; Ping He, PhD, Sun Health Research Institute; and Virginia Lee, PhD, University of Pennsylvania School of Medicine. The study was supported by grants from the National Institutes of Health, National Institute of Aging, and the John D. French Alzheimer’s Foundation.

Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine. MGH and Brigham and Women's Hospital are founding members of Partners HealthCare HealthCare System, a Boston-based integrated health care delivery system.