Effects of blood plasma transfusion from young mice to h-Tau mice modeling Alzheimer's disease



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Aging is characterized by a decline in synaptic plasticity and cognitive functions. This is intensified in Alzheimer’s disease by the buildup of plaques and tangles in the brain. The tangles contain a stabilizing protein called tau, that detaches from a collapsing neuron and clump together in the intracellular space, thus called tau tangles. There are limited treatments for Alzheimer’s disease, therefore the exploration of new alternatives is warranted. In a recent study, plasma was transfused from young mice to older transgenic mice containing plaques, causing an improvement in new spatial learning and memory tasks and an increase in proteins that support synaptic plasticity of neurons (Middeldorp et al. 2016). Because mice with tau tangles in the brain were not included in this design, we proposed to transfuse plasma from young wild-type mice to older transgenic mice that can develop tangles expressing human tau (h-Tau, P301L/CaMKII), followed by an examination of behavioral outcomes and tau pathology of the older mice. Mice were given eight 150l injections of either plasma or saline over a course of a week. Overall, h-Tau mice regardless of injection, performed poorly in Morris water maze (MWM), built poorer nests, burrowed less, and had an irregular circadian rhythm compared to wildtype mice regardless of injection. Although at the cellular level, h-Tau mice injected with plasma had lesser expression of phosphorylated tau in the brain compared to h-Tau mice injected with saline. Accordingly, h-Tau mice injected with plasma had fewer tau tangles in the cortex, CA1 region of the hippocampus and smaller tau tangles in the cortex compared to h-Tau injected with saline. Although young blood plasma was not able to rescue behavioral impairments caused by tau tangles, it still provides promising results which open the door to other future studies revolving young blood plasma transfusions.