Over The DAM: Cells That Rejuvenate The Brain

Alzheimer’s disease is a neurodegenerative disease manifested by various neuronal pathological processes and a significant decline in brain function. Aggregates of beta-amyloid protein (“plaques”) accumulate within the brain cells and between them. Due to both structural changes and the weakening of chemical communication pathways, the junctions of neuronal networks (synapses) are lost. In addition, the cytoskeletal proteins of the axons lose their normal structure, impairing their function and causing massive neuronal death. The brain is a fragile and unique organ that has its own specially tailored immune system separated from the rest of the body. The primary role of these immune cells, called microglia, is to recognize, disassemble and dispose of various substances that do not function properly in the brain, from dying cells to various cell debris and protein aggregates. Yet microglia activity is under tight regulation to allow them to dispose of waste without harming adjacent healthy neurons that retain important information. The gamut of their activity — from essential immune function to the risk of damaging healthy neurons due to hyperactivity — is well balanced in young healthy individuals, but might become a disadvantage in aging and under neuropathological conditions. A key question is why are the brain’s resident immune cells not effective in repairing the damage associated with Alzheimer’s disease?

Alzheimer’s disease is often associated with local inflammation. In the absence of a clear understanding of the contribution of the systemic and brain immune cells to disease pathology, many scientists have interpreted the local brain inflammation that accompanies Alzheimer’s disease as a negative outcome of excessively aggressive microglia and the uncontrolled entry of immune cells from the periphery into the brain. Anti-inflammatory treatments were therefore attempted, without success, leaving the researchers in the field puzzled as to the function of immune cells in neurodegenerative diseases.

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