Grant: Project Grant

There is currently no treatment to prevent or cure Alzheimer's disease (AD), the most common cause of dementia. To achieve this goal, we first need to identify biological markers to detect the disease as early as possible, before neurodegeneration produces irreversible brain damage and severe cognitive deficits that prevent patients from functioning independently. It is well-established that AD dementia is preceded by a transitional stage with amnestic mild cognitive impairment (aMCI). Since the loss of contact (synapses) between brain cells (neurons) is observed in aMCI, this project aims to determine if the synaptic proteins neuroligin-1 and neuroligin-2 are effective blood biomarkers for aMCI. We have developed an ultra-sensitive mass spectrometry approach to determine the levels of these proteins in the blood of aMCI and early AD subjects compared to age-matched control elderly. Thanks to seed funding that we obtained previously from the Weston Brain Institute, we were able to collect very exciting and promising preliminary data showing that neuroligin-1 and neuroligin-2 might represent novel and specific blood biomarkers of early AD. Although we observed significant differences in the levels of these proteins between AD, aMCI, and control participants, our study was limited by the number of samples in each group. Therefore, we are planning to extend our findings in larger and well-characterized cohorts before considering the use of these biomarkers in clinical practice and trials. RELEVANCE: Since blood-based biomarkers are simple, minimally invasive, and cost-effective, they have the potential to revolutionize clinical practice and clinical trials in the field of AD. Measuring blood levels of neuroligin proteins could directly impact the translational development of therapeutics by using these biomarkers as a screening tool to detect aMCI more efficiently and to monitor disease progression in clinical practice and trials.