Study Examines If Cancer Drugs Can Transform Alzheimer's Care - Video

The study published in the journal Science proposes that inhibiting the kynurenine pathway-a key regulator of brain metabolism-could enhance or even restore cognitive function in Alzheimer’s disease by restoring normal brain metabolism.

Neuroscientists believe that Alzheimer’s disease might damage brain function by interfering with glucose metabolism, which is essential for maintaining a healthy brain. Essentially, reduced metabolism deprives the brain of the energy it needs, leading to problems with thinking and memory.

A team of neuroscientists has focused on the kynurenine pathway, a key regulator of brain metabolism. They suspect that this pathway is overactivated due to the buildup of amyloid plaques and tau proteins in the brains of Alzheimer’s patients. Researchers have demonstrated that blocking the kynurenine pathway in lab mice with Alzheimer’s Disease can enhance or even restore cognitive function by reestablishing normal brain metabolism.

In the brain, kynurenine plays a role in producing lactate, an energy molecule that supports neurons and maintains healthy synapses. Scientists focused on the enzyme indoleamine-2,3-dioxygenase 1 (IDO1), which produces kynurenine. They hypothesized that elevated levels of IDO1 and kynurenine, driven by the buildup of amyloid and tau proteins, would disrupt normal brain metabolism and cause cognitive decline. By inhibiting IDO1 and thus reducing kynurenine production, they found that the ability of astrocytes to supply neurons with lactate was restored.

indoleamine-2,3-dioxygenase 1 is well-established in oncology, and there are already drugs undergoing clinical trials to inhibit indoleamine-2,3-dioxygenase 1 activity and reduce kynurenine production. This allowed scientists to bypass the lengthy process of developing new drugs and start testing existing ones in lab mice right away.

The next step for scientists is to evaluate indoleamine-2,3-dioxygenase 1 inhibitors in human Alzheimer’s patients to determine if they lead to similar improvements in cognition and memory. Previous clinical trials focused on the use of indoleamine-2,3-dioxygenase 1 inhibitors for cancer treatment did not assess or expect any effects on cognitive function.

Scientists are looking forward to exploring IDO1 inhibitors in upcoming human trials specifically for Alzheimer’s disease.

Reference: Paras S. Minhas et al., Restoring hippocampal glucose metabolism rescues cognition across Alzheimer’s diseasepathologies.Science385,eabm6131(2024).DOI:10.1126/science.abm6131