Developing a Cell Therapy for Alzheimer's Disease

Delivering new neurons to replace those lost in Alzheimer's disease isn't an ideal approach in isolation: it is a patch therapy, something that doesn't attempt to address the root causes of the condition in any way, and thus can have only limited short-term benefits while those causes are still churning away. However this sort of treatment may be needed for people that have advanced Alzheimer's disease at the time a cure is finally deployed. The clinical community will need some way to restore function in those who have suffered irreversible damage in the late stages of the condition.

Scientists transplanted inhibitory neuron progenitors - early-stage brain cells that have the capacity to develop into mature inhibitory neurons - into two mouse models of Alzheimer's disease, apoE4 or apoE4 with accumulation of amyloid beta, another major contributor to Alzheimer's. The transplants helped to replenish the brain by replacing cells lost due to apoE4, regulating brain activity and improving learning and memory abilities. "This is the first time transplantation of inhibitory neuron progenitors has been used in aged Alzheimer's disease models. Working with older animals can be challenging from a technical standpoint, and it was amazing to see that the cells not only survived but affected activity and behavior."

A balance of excitatory and inhibitory activity in the brain is essential for normal function. However, in the apoE4 model of Alzheimer's disease - a genetic risk factor that is carried by approximately 25% of the population and is involved in 60-75% of all Alzheimer's cases - this balance gets disrupted due to a decline in inhibitory regulator cells that are essential in maintaining normal brain activity. The hippocampus, an important memory center in the brain, is particularly affected by this loss of inhibitory neurons, resulting in an increase in network activation that is thought to contribute to the learning and memory deficits characteristic of Alzheimer's disease. The accumulation of amyloid beta in the brain has also been linked to this imbalance between excitatory and inhibitory activity in the brain.

In the current study, the researchers hoped that by grafting inhibitory neuron progenitors into the hippocampus of aged apoE4 mice, they would be able to combat these effects, replacing the lost cells and restoring normal function to the area. Remarkably, these new inhibitory neurons survived in the hippocampus, enhancing inhibitory signaling and rescuing impairments in learning and memory. In addition, when these inhibitory progenitor cells were transplanted into apoE4 mice with an accumulation of amyloid beta, prior deficits were alleviated. However, the new inhibitory neurons did not affect amyloid beta levels, suggesting that the cognitive enhancement did not occur as a result of amyloid clearance, and amyloid did not impair the integration of the transplant.

Link: http://gladstoneinstitutes.org/pressrelease/2014-07-15/transplantation-of-healthy-new-brain-cells-reverses-learning-and-memory-loss

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