Sara Calafate´s Alzheimer Project published in Nature Neuroscience

ICVS´s researcher Sara Calafate saw her work on Alzheimer’s disease recognized and published in Nature Neuroscience.

Sara Calafate, Joris de Wit and Bart de Strooper at the VIB-KU Leuven Center for Brain & Disease Research, co-led a project that involved the lab of Tiago Gil Oliveira at ICVS, and investigated an interesting phenomenon in a mouse model of Alzheimer’s disease.

Even though Alzheimer’s disease (AD) patients remain cognitively stable in early disease stages they start to accumulate amyloid-beta and tau toxic aggregates.  Interestingly, during this early phase of the disease, patients can experience sleep problems. Moreover, abnormal brain activity resembling epilepsy develops, but this goes often unnoticed by patients and doctors. In particular, neuronal activity increases in the hippocampus, which is a brain region crucial for memory. Despite this, patients’ cognitive abilities stay relatively intact for a long period of time but the mechanisms that maintain this stability eventually fail and cognitive defects become stronger.

Using a technique called spatial transcriptomics, this research team identified that a neuropeptide called melanin-concentrating hormone (MCH) is involved in the pathogenesis of AD. They found that MCH-peptide, a peptide known to control sleep, is able to reduce the activity of neurons in the hippocampus. Moreover, they found that an AD mouse model shows a decrease in the activity of the neurons that produce MCH and also in their ability to sleep. Interestingly, this mouse model displays increased neuronal activity in the hippocampus, which was rescued by MCH incubation. Furthermore, they showed that MCH neurons are damaged in brains of Alzheimer’s patients. These findings highlight the importance of the MCH system in the early stages of Alzheimer’s disease and indicate that the failure of MCH neurons contributes to a loss of neuronal stability in the brain. This paves the way for novel therapies involving the MCH system, that aim to stabilize brain activity in early stages of Alzheimer’s disease.