Human CNS immune senescence and neurodegeneration

• Evidence indicative of microglial senescence in humans is summarized.
• It is proposed that microglial senescence is linked to diminished neuroprotection.
• It is proposed that neurofibrillary degeneration occurs because of microglial senescence.
• The idea that inflammation causes neurofibrillary degeneration is questioned.

Microglial cells comprising the brain's immune system are essential for ensuring neuroprotection in the normal and pathological CNS. On the basis of histopathological observations in human brain, we believe that the ability of microglia to provide neuroprotection deteriorates as our brains get older and that such CNS immune senescence is a major factor contributing to the development of aging-related neurodegenerative diseases, notably Alzheimer's disease. The idea is consistent with the fact that immune senescence occurs naturally in the periphery, rendering the elderly people more susceptible to infections and cancers. There is an analogous situation in the brain, except that here the main impact comes down to diminished neuroprotection and resultant neurodegeneration.