Researchers find protein abnormality associated with Alzheimer's disease

The protein agrin could play a distinctive role both in the early and later stages of Alzheimer's disease, according to a new study in the current Proceedings of the National Academy of Sciences.

PROVIDENCE, R.I. -- Brown University researchers say that a protein widespread in the nervous system is also found in plaques and other brain lesions associated with Alzheimer's disease, a finding that may contribute to a clearer understanding of why and how the disease occurs.

The protein, called agrin, is involved in the development of the nervous system. The researchers suggest that agrin may also play a role in the development of nerve cell connections in the brain, which could be altered in Alzheimer's disease.

The study finds that agrin is present in the human brain and that the protein's distribution and biochemical properties are altered in the brains of Alzheimer's disease patients.

The researchers demonstrate that agrin abnormalities are linked with plaques associated with Alzheimer's disease. Such plaques are local brain lesions characterized by injured cells and the accumulations of an abnormal protein called beta-amyloid. Biochemical evidence in the study indicates that agrin is closely linked with deposits of beta-amyloid protein and may be bound to them.

"These observations suggest that agrin could play a distinctive role both in the early and later stages of the development and progression of Alzheimer's disease," said Edward Stopa, M.D., one of the study authors and an associate professor of pathology.

The study appears in the current Proceedings of the National Academy of Sciences.

Alzheimer's disease is a degenerative disorder in the brain characterized by progressive memory loss and cognitive deficits. The disease has yet to be explained and no cure is known.

The study's principal authors are John Donahue, M.D., a neuropathology fellow; Tyler Berzin, a senior undergraduate; and Michael Rafii, an M.D.-Ph.D. student. The study was performed in Stopa's lab at Rhode Island Hospital and the lab of Justin Fallon, associate professor of neuroscience. Other authors include David Glass and George Yancopoulos, scientists at Regeneron Pharmaceuticals in Tarrytown, NY.

In previous research, Fallon showed that agrin contributes to development of the connection between nerve and muscle cells. Agrin causes "clustering" of neurotransmitter receptors on the muscle cell, to ensure proper communication with the nervous system.

All experiments in the study being reported this month were performed on post-mortem brain tissue donated to the Brown University Brain Bank. The study was supported by grants from the National Institutes of Health.