Italian researchers have discovered a new gene that causes Alzheimer's Disease, according to a study published in the international scientific journal Alzheimer's Research & Therapy.
This research is the result of collaboration among several Italian research groups, coordinated by the Molinette hospital of the Città della Salute in Turin. The study suggests that rare genetic mutations may also contribute to the disease in older adults, as explained by Innocenzo Rainero, who directs the Alzheimer's and related dementia Center at the Molinette hospital and the University of Turin.
The scientific group, led by Dr. Elisa Rubino, studied an Italian family with senile-onset Alzheimer's disease, identifying mutations in the Grin2C gene, which codes for a subunit of the NMDA glutamate receptor. This was achieved using advanced molecular genetic techniques.
The researchers demonstrated that this mutation increases neuronal excitability and alters the binding of the Grin2C protein with other neuronal proteins. Rainero noted that until now, rare mutations in the Psen1, Psen2, and App genes were known to cause Alzheimer's disease, primarily in presenile age. He had previously contributed to the identification of Psen1 in 1995.
Rubino stated, "We expect Grin2C to be a very rare cause of Alzheimer's disease," emphasizing the significant aspect of the research: the confirmation of the role that glutamate-related excitotoxicity mechanisms may have in the disease's development. When glutamate interacts with the NMDA receptor on neurons, a channel opens that allows calcium ions to enter. Excessive stimulation can lead to intense neuronal excitation and cell death.
Clinically, it is noteworthy that before cognitive deficits develop, patients carrying the mutation may experience depressive mood disorders for years. The study indicates that new drugs capable of reducing glutamate-induced cerebral excitotoxicity will be necessary to slow the progression of this serious disease.
The research involved collaboration with Elisa Giorgio from the Department of Molecular Medicine at the University of Pavia, Alfredo Brusco from the Department of Neuroscience at the University of Turin, and Fabrizio Gardoni from the Department of Pharmacology and Biomolecular Sciences at the University of Milan. Alzheimer's disease is the leading cause of severe cognitive deficits and has become a major global health concern, resulting from a complex interaction of genetic and numerous environmental factors, such as hypertension, obesity, diabetes, depression, and social isolation, which contribute to the deposition of toxic proteins, beta-amyloid and tau protein, in the brain, responsible for neurodegeneration.