Wednesday, October 21, 2020

The Role of Microglia in Alzheimer's and Parkinson's Diseases

 

Alzheimer’s and Parkinson’s are diseases that directly impact and impair brain functions. They are degenerative and devastating illnesses that result in severe dementia in the case of Alzheimer’s and a serious degradation of motor control in the case of Parkinson’s disease. There is no cure in either case and no known biomarkers that could predict onset of these conditions. There is a type of cell resident in the brain referred to as microglia that function as amyloid phagocytes – they are cells capable of monitoring the local environment and can ingest and clear amyloid protein.

It seems that in addition to this known role, microglia may play an additional and essential role in maintaining neuronal function and homeostasis. In fact, the build up of amyloid protein in brain tissue may not be the primary cause of dementia that is the result of neuronal dysfunction and cognitive decline in neurodegenerative disease – some centenarians have been found to display good cognitive health and a build up of amyloid proteins in their brain tissue. It seems that accumulated patient data demonstrate that some aging individuals with accumulated amyloid protein show cognitive dysfunction while others do not. It is important from a therapeutic standpoint to understand the nature of this difference.

Several genetic studies indicate that microglia may provide the answer to this difference in health outcomes. According to Soyon Hong from the UK Dimentia Research Institute at University College, London, “Emerging data in developing, adult, and diseased brains collectively suggest that microglia are critical to neuronal homeostasis and health. These observations raise the question of whether, and which, microglia-neuron interactions may be impaired in Alzheimer’s disease (AD) and Parkinson’s disease (PD) to confer neurodegeneration. Insight into this question will enable the development of methods to assess and modulate microglia-neuron interactions in the aging brain and allow for a desperately needed expansion of focus from clearing amyloids alone to monitoring neuronal health in biomarker and target engagement efforts.”

It seems that in addition to their role in clearing pathogens and amyloid protein and responding to the presence of injury and dying neurons present in the environment of the brain, microglia are involved in monitoring changes in neuronal activity and the modulation of such distinct functions as memory and learning. In AD, for example, synaptic loss and dysfunction have been shown to be associated with the disruption of cognitive ability in patients. It is, therefore, of great importance to understand the underlying mechanisms that are responsible for this degenerative process and the role that microglia play in maintaining synaptic integrity.