The accumulation of a fragment of the synaptic protein neurexin in adult brains leads to specific memory losses in Alzheimer’s disease patients. The findings are a step forward in understanding the catalysts of memory loss in the debilitating condition.
Researchers from the “Synaptic Dysfunction and Disease” group at the Institute of Biomedicine of Seville (IBiS) say they’ve also made advances in the study of neurexin in patient samples. The progress is aimed at preventing the protein from accumulating and causing the observed Alzheimer’s symptoms.
In their study, researchers concentrated on a neurexin protein fragment, known scientifically as NrxnCTF. Presenilin function is critical to normal synaptic functioning and memory in the brain. Mutation in Presenilin genes (the genes associated with familial forms of Alzheimer’s disease) causes accumulation of NrxnCTF, leading to loss of memory as observed.
In animal models, experimental accumulation in the adult brains of mice also triggered this reaction, as well as other memory defects. The experimental models of Alzheimer’s disease as used in this study are key in identifying pathogenic mechanisms as well as developing effective therapy options.
Behavioral studies showed that the accumulation of NrxnCTF led to a loss of associative memory that depends on the amygdala, a part of the brain associated with the processing of memory, emotions, and decision making. Researchers used electrophysiological recordings to observe synaptic connections from the prefrontal cortex to the amygdala in mice, finding defects in presynaptic plasticity as a result of NrxnCTF accumulation.
Overall, the data clearly demonstrates that NrxnCTF is a relevant variable that causes the inhibition of Presenilin function. This newfound knowledge of the functional impact in the loss of Presenilin function may represent a noteworthy step in Alzheimer’s disease, leading experts to more effective treatments.
This project was funded by the Andalusia Regional Government’s Department of Innovation, Science and Business and the Spanish Ministry of Science, Innovation, and Universities.
This study is published in Experimental Neurology.
Article written by Anna Landry