We test the monkeys with cognitive tasks while they are aging and note savings and cognitive decline over time in each task (working memory, visual search, rule shifting). Then after they have reached their natural end of life, we examine their brain tissue post-mortem to note levels of neurons, astrocytes, and microglia in different key structures involving memory, attention, and executive function. We look for the presence of beta-amyloid species, including plaques, and phosphorylated tau in these same areas. We have also started to examine whether neurogenesis is occurring in different areas of the brain. All of these should correlate with cognitive decline found in life, to some degree, but some may illuminate the relationships between immune responses (astrocytes and microglia), misfolded proteins that may interfere with cell function and communication across synapses (beta-amyloid and tau), neural death and neurogenesis. The combination of knowing the neural signature or portrait of each monkey with knowing how much decline they experienced should elucidate how cognition may show savings or loss as a function of how these systems are reacting to aging. There may be some neurodegenerative disease revealed in some of these aging monkeys, and the addition to aging of disease is an important matter to address. There is evidence that tamarins may be a model of Alzheimer’s Disease because they naturally accumulate beta-amyloid plaques late in life (Lemere et al, 2009).
We have presented 2 posters at national conferences, one in 2018 which only examines some of the physiological variables in 4 monkeys that died at different ages, and one in 2019 in which we could do a more thorough individual assessment of cognitive ability with physiological state and neuropathological threats. Our plan is to complete analyses like these with all of our monkeys.
A cognitive and neuropathological analysis of one aged monkey, Wisteria, age 20 at time of death, presented at the Society for Neuroscience (2019).
An analysis of the presence of AD markers and astrocyte function in 4 different aged monkeys, presented at the Society for Neuroscience (2018).