Biomarkers for Monitoring Memory Enhancing Drugs
The Laboratory for Translational Research in Neuropsychiatry at the CUNY School of Medicine combines behavior, biochemistry, electrophysiology, neurogenesis and neurophysiology in human subjects with parallel studies in humans. Based upon recent findings, synaptic dysfunctions and abnormal neuroplasticity are becoming new and attractive hypotheses to explain the pathogenesis of AD and appear to be promising therapeutic targets. The Lab and its collaborators showed a deficit on N-methyl-D-aspartate receptor (NMDAR)-dependent neocortical plasticity in mild-to moderate AD patients at the same time demonstrating that 4-4.5 month old mice overexpressing amyloid precursor protein (APP) (K67ON:M671L) together with presenilin-1 (PS1) (M146L) matched to the same stage of AD progression display reduced Long Term Potentiation (LTP) and have marked alteration of NMDAR activity. These results provide the unique possibility of using the same biomarkers to monitor memory enhancing drugs in the AD animal model and in patients with AD.
Rapid, Efficient In Vitro System for Screening Drug Efficacy in AD
Even in the fastest AD animal model pathology does not start before the end of the second month making it necessary to wait at least until this age to inject drugs to assess whether they prevent, reduce or prevent synaptic impairment, plaque formation and increase beta-amyloid levels. This culture system comprises hippocampal neuronal and glial cells from animal models of AD. The effects of a test substance on the cells in the culture system can be quantitatively assessed to determine if the test substance affects the cells biochemically, electrophysiologically, or immunocytochemically. At the same time the culture system pro ides a tool for production of amyloid-beta that can be used for electrophysiological, behavioral, and toxicological studies. This assay allows drug testing efficacy at single cell level, in the animal model (behavior, neurophysiology, biochemistry) and in patients (brain simulation and neuroimaging) using biomarkers of synaptic plasticity.