Researchers at the Gladstone Institute of Neurological Disease (GIND) and Baylor College of Medicine have uncovered a potential mechanism behind the impairment of neurological functions in Alzheimer's disease.
The scientists say that they have found that the protein Amyloid-beta (A-beta) triggers abnormal over-excitation of the brain networks that are responsible for learning and memory.
Advertisement"Such abnormal network activity in Alzheimer's patients was thought to be a collateral or secondary event caused by the degeneration of nerve cells," said Dr. Jorge J Palop, Gladstone research scientist, and lead author of the study published in the journal Neuron.
"But our study suggests that this activity may actually be a primary effect of A-beta and an early determinant of cognitive failure," Dr. J. Palop added.
The researchers genetically engineered mice with a human gene that causes high levels of A-beta. Upon experimentation with the mouse models, they discovered that high levels of the protein induced an insidious type of seizure activity in learning and memory centres, which was not accompanied by the usual twitching and jerking movements seen in many forms of epilepsy.
In fact, it took sophisticated brain wave recordings in freely behaving mice by electroencephalography (EEG) and telemetry to detect the seizure activity.
"We were really surprised by these findings because A-beta had previously been suspected to primarily suppress neuronal activity," said Dr. Lennart Mucke, GIND director and professor of neurology and neuroscience at the University of California, San Francisco (UCSF), and senior author of the study.
"This abnormal brain activity could play an important role in the development of Alzheimer-related cognitive impairments," the researcher said.
The researchers say that their findings raise the disconcerting possibility that Alzheimer patients may also have non-convulsive seizures that could easily escape detection by standard clinical exams.
They now plan to test their hypothesis in follow-up study of human subjects.
"Our results have important therapeutic implications, because the prevention and reversal of non-convulsive seizure activity has not yet been a major focus of clinical trials in Alzheimer's disease. Our results suggest that the suppression of this activity might prevent and possibly even reverse cognitive impairments induced by high levels of A-beta," said Dr. Mucke.