Stopping cell decay may delay Alzheimer’s

MCGILL (CAN) — Researchers have uncovered a critical process in the degeneration of brain cells sensitive to Alzheimer’s disease, a discovery that may help develop alternative therapies for the disease.

A breakdown in communication between the brain’s neurons is thought to contribute to the memory loss and cognitive failure seen in Alzheimer’s patients.

The likely suspect is nerve growth factor (NGF), a molecule responsible for generating signals that maintain healthy cholinergic neurons—a subset of brain cells that are particularly sensitive to Alzheimer’s throughout a person’s lifetime. But scientists had never been able to find anything wrong with the molecule to explain the degeneration of cholinergic neurons.


Published in the Journal of Neuroscience, the new study elucidates the process by which NGF is released in the brain, matures to an active form, and is ultimately degraded.

The researchers were also able to determine how this process is altered in Alzheimer’s. Treatment of healthy adult rats with a drug that blocks the maturation of active NGF leads to Alzheimer’s-like losses of cholinergic functional units, which result in cognitive impairment.

By contrast, when treated with a drug to prevent degradation of active NGF, the numbers of cholinergic contacts increased significantly.

“Part of the difficulty in understanding this pathway has been due to the technical challenges associated with differentiating the active and inactive forms of NGF,” says Simon Allard, postdoctoral fellow at McGill University and the study’s lead author. “Our proposed manipulations are different from existing therapies as they aim to protect neurons from degeneration.”

The authors suggest that these findings may lead to pharmacological treatments that could delay the progression of Alzheimer’s disease.

“This discovery should help design alternative therapies,” says Claudio Cuello, professor of pharmacology and therapeutics.

The study was supported by the Canadian Institutes of Health Research (CIHR) and an endowment from Alan Frosst and the Frosst family.

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