Massachusetts General Hospital

They then found how this calcium overload probably interferes with neuronal communication.  Normally specific signals being transmitted are reflected by distinct calcium levels in structures called dendritic spines, but in mice with the plaque-associated elevations, calcium levels were the same throughout a dendrite instead of changing at the locations of the spines.  Those dendrites in which calcium levels were highest also had structural changes similar to those seen in the brains of patients who have died with Alzheimer’s disease.

Cellular calcium overload can damage cells through a pathway involving the action of an enzyme called calcineurin, and a previous study found that treatment with a calcineurin inhibitor appeared to improve cognition in an Alzheimer’s mouse model.  After the MGH-MIND team treated plaque-bearing mice with the same calcineurin inhibitor, they found that neuronal calcium levels were  partially moderated and dendrites did not continue to degenerate, indicating that the calcineurin pathway may be a potential therapeutic target.

“We need to keep in mind that animal models are not a complete reflection of what happens in human disease, so we can’t extrapolate too far down the road,” Bacskai says.  “But our data do suggest that calcineurin inhibition should be investigated in future studies, which also should look at how amyloid-beta causes calcium overload and whether removing plaques really does improve neuronal health.”  He also noted that dietary calcium has no effect on the cellular calcium levels examined in this study, so people concerned about the risk of Alzheimer’s should not hesitate to take calcium supplements to address other health issues.

Bacskai is an associate professor of Neurology at Harvard Medical School.  The first author of the Neuron report is Kishore Kuchibhotla, a doctoral student in the Harvard University Biophysics program; additional co-authors, all from MGH-MIND, are Samuel Goldman, Carli Lattarulo, Hai-Yan Wu, PhD, and Bradley Hyman, MD, PhD. The work was supported by grants from the National Institutes of Health.

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.