A new discovery at the Yale School of Medicine has uncovered a key component to understanding and curing Alzheimer’s disease.

The neurofibrillary tangling and degradation of links between neurons characteristic of Alzheimer’s is the result of a long chain of protein interactions that has intrigued researchers for decades. Scientists at the Medical School have recognized a receptor called metabotropic glutamate receptor 5, or mGluR5, as the missing link in the chain of biological processes leading to Alzheimer’s disease. The findings on mGluR5 were published in the journal Neuron on Sept. 4.

The team knew the coupling of amyloid-beta and prion proteins was an influencing factor in the development of Alzheimer’s, but the scientific community was previously unable to discern how the interaction of these proteins — which occurs outside the neuron cell — were able to affect the cell’s inner environment. The study showed that the mGluR5 receptor serves as a binding site for the prion protein, triggering the release of an intracellular protein causing tangling.

The receptor not only serves as a link in the chain of events causing Alzheimer’s — the discovery makes possible the creation of new drugs to treat the actual disease rather than just its symptoms.

“The treatments we have as of today for Alzheimer’s perform very little on a day-to-day basis of helping to reduce symptoms and are unable to stop the disease and prevent real damage,” said senior author of the study Stephen Strittmatter, a Yale School of Medicine neurology professor.

The researchers had previously conducted research on the mGluR5 receptor in relation to Fragile X Syndrome, a genetic condition causing mental disabilities. Since they knew the mGluR5 receptor is responsible for brain plasticity and learning, they were able to test drugs created to treat Fragile X Syndrome on mice with Alzheimer’s disease who exhibited similar cognitive impairments. These drugs blocked the prion protein from binding to the mGluR5 receptor, therefore preventing the formation of neurofibrillary tangles. A mouse model of Alzheimer’s showed clear signs of restoration in memory, learning and synapse density when the research team employed the drug.

“The beauty of mGluR5 is that it is a perfect target for drug treatment,” said study author Erik Gunther, an associate research scientist in neurology.

Though the mice trials give the research team hope for the possibility of an Alzheimer’s treatment, they said years of experimental trials are necessary to attain FDA approval. When too much of the drug was administered to the mice, their condition became worse, and when the mice received low dosages, the drug was not helpful, he added. Consequently, the research team is trying to engineer a completely new drug.

Strittmatter said creating a successful drug can pose difficulties.

“The drugs [treating Fragile X Syndrome] now block both the abnormal and normal functions of the mGluR5,” Strittmatter said. “Thus, the correct dosage is necessary because if you were to shut down the whole receptor then you lose the normal biological necessities of the receptor.”

Study authors said the discovery of mGluR5 is not the final frontier in Alzheimer’s research — creating a drug to treat it is.

“Alzheimer’s is an incredibly huge health problem,” Strittmatter said. “Alzheimer’s is one of the few diseases which mortality rates keep increasing because not enough funds or attention have been devoted toward research.” The team does have hope but they are disheartened by the lack of public attention toward such a prevalent health issue in today’s society, he added.

Over 5.1 million people in the United States have Alzheimer’s disease, according to the National Institutes of Health.