Recent McGill research may have brought scientists one step closer to finding an early marker for Alzheimer’s disease.
Alzheimer’s is one of the most menacing chronic illnesses, one which attacks the brain by degrading the neural tissue necessary for thoughts and normal brain function. The disease manifests by erasing the self, as the memories, relationships, and beliefs central to one’s identity are eroded. Friends and family are left to watch helplessly as loved ones succumb to Alzheimer’s, haunted by the fact that despite the advancements of modern medicine, nothing can be done to stop its progression.
With an aging population, it is predicted that the number of Alzheimer’s cases in North America will roughly triple by 2050. This poses a great burden to our health care system-currently, the pathology of the disease is still not fully understood, which complicates the search for effective treatments. To make matters worse, the degeneration of the brain is asymptomatic. An Alzheimer’s diagnosis carries with it a degree of hopelessness, because existing therapies have proven to be only mildly effective, being unable to target the underlying condition.
What is understood is that the cortical cholinergic system plays a prominent role in cognitive processing and that a progressive degradation of this system is partly responsible for the cognitive impairment associated with Alzheimer’s disease. A molecule called the Nerve Growth Factor (NGF) has previously been identified as a protector of these cholinergic neurons.
Research led by Dr. A. Claudio Cuello of McGill’s department of pharmacology and therapeutics found an imbalance in the metabolism of NGF in Alzheimer’s-afflicted brains. NGF is secreted in an inactive form, and must change form outside the cell in order to become functional. In brains with Alzheimer’s, this maturation process is compromised and NGF is degraded.
Cuello and his team attempted to reproduce this imbalance in rats.
“[We wanted to] validate that this pathway is indeed responsible for maintaining the cholinergic phenotype in the Alzheimer’s system,” he said.
They pharmacologically blocked the NGF maturation pathway, forcing an accumulation of the inactive form. They found that this disruption led to the degeneration of cholinergic neurons and the onset of Alzheimer’s-like cognitive impairment. Conversely, when the degradation of mature NGF was inhibited by drug intervention, there was a significant increase in cholinergic contacts which are required for proper neuronal communication, demonstrating that NGF is crucial for the health of these neurons. This is an enormous breakthrough which points toward the regulation of NGF as a potential Alzheimer therapeutic target.
Dr. Cuello identified a few barriers in place that must be resolved before NGF-targeting drugs can be developed. First, there is no marker that allows us to diagnose Alzheimer’s because it is asymptomatic when loss of neural tissue is already taking place. This is the one of greatest obstacles that scientists need to overcome. Since there is no tell-tale sign, it is very difficult to target those who are at risk and to determine what stage they are at during neural decline.
In order to attack the underlying condition and stop the progression of the disease in its tracks, a patient must receive proactive treatment prior to the onset of any symptoms. In addition, there need to be drugs targeted to specific parts of the brain, because the secretion of NGF is spatially specific, meaning that the drug cannot be applied universally. The drugs applied to animal models in this study were very powerful and unsuitable for human intervention as they could produce adverse effects.
In spite of these roadblocks and the difficult nature of Alzheimer’s disease, Dr. Cuello noted that many researchers are striving to discover pre-clinical indicators of the disease, which once identified, will reveal the brain’s hidden sickness and provide patients with necessary time to take action.
“We are in a position of optimism,” Cuello said.
