Synaptic function as a preclinical and experimental medicine readout for disease-modifying therapy in Alzheimer's Disease

Alzheimer's disease is a growing disease burden that affects millions of people worldwide and is expected to double by the year 2030 as the current standard of care only partially treats the symptom. A disease modifying treatment is in urgent need. A major challenge is to demonstrate disease-modification in the clinic, as the current treatment measures monitor mostly pathological biomarkers that are not linearly related to the clinical disease. Since synaptic dysfunction is directly related to cognitive deficits even in early stages of cognitive impairment, attempts are in progress to directly measure synaptic function non-invasively and some of the tools and pharmacological agents to measure synaptic function both in clinic and preclinical models are reviewed here. Finally, we propose measuring synaptic function could be used as an experimental medicine readout while testing disease-modifying agents in the clinic.