Italian researchers have identified a new gene linked to Alzheimer’s disease, marking a significant breakthrough, according to a study released on Sunday.
The study, published in Alzheimer’s Research & Therapy, highlights the discovery of mutations in the Grin2C gene, which codes for a subunit of the Nmda glutamate receptor.
“This was great teamwork,” said Innocenzo Rainero, head of the Alzheimer’s Centre at Turin’s Molinette hospital. “We actively collaborated with the Universities of Pavia and Milan. The all-Italian team worked together for seven to eight years since we first began studying the patients.”
Rainero explained, “With next-generation sequencing, which allows us to sequence large genomes quickly, we isolated a rare mutation — like finding a needle in a haystack.”
The researchers focused on a family with specific genetic traits. “After this discovery, we will verify the frequency of these mutations in other Alzheimer’s patients and study glutamate’s role as a therapeutic target,” Rainero noted.
Glutamate essential for memory
Dr Elisa Rubino, who led the research, emphasised the significance of understanding glutamate-related excitotoxicity in Alzheimer’s. “Glutamate, the most important excitatory neurotransmitter, is crucial for memory. However, excessive release has a toxic effect on neurons,” she explained.
The study demonstrated that this toxic effect also involves other neuronal proteins. “This highlights the role of this neurotransmission system in disease development,” added Rainero.
Alzheimer’s is an extremely heterogeneous disease, according to Rainero. “There is a genetic predisposition in most cases, but gene variants are rare. Even so, this rare mutation helps us understand the disease mechanisms.”
Clinically, the team observed that patients with the mutation often developed depressive mood disorders before cognitive decline.
The study suggests that new drugs targeting glutamate-induced excitotoxicity could slow Alzheimer’s progression. Rainero emphasised the need for a multidimensional approach to treatment, combining prevention, early diagnosis using biomarkers, and pharmacological strategies targeting various mechanisms, including glutamate excitotoxicity.
The research involved collaboration with Elisa Giorgio from the University of Pavia, Alfredo Brusco from the University of Turin, and Fabrizio Gardoni from the University of Milan. Alzheimer’s remains a leading cause of cognitive decline and a significant global health challenge, driven by complex interactions between genetic and environmental factors.
