Microglia in Alzheimer Brain: A Neuropathological Perspective

Microglia have long been noted to be present and activated in Alzheimer brain. Demonstrations that these microglia are associated with the specific lesions of Alzheimer disease—Aβ plaques and neurofibrillary tangles—and that these microglia overexpress the potent proinflammatory cytokine interleukin-1 led to the recognition of a potential pathogenic role for these cells in initiation and progression of disease. Activated, cytokine-overexpressing microglia are near-universal components of Aβ plaques at early (diffuse) and mid (neuritic) stages of progression in Alzheimer brain, and only decline in end-stage, dense core plaques. They correlate with plaque distribution across cerebral cortical cytoarchitectonic layers and across brain regions. They also show close associations with tangle-bearing neurons in Alzheimer brain. Microglial activation is a consistent feature in conditions that confer increased risk for Alzheimer disease or that are associated with accelerated appearance of Alzheimer-type neuropathological changes. These include normal ageing, head injury, diabetes, heart disease, and chronic intractable epilepsy. The neuropathological demonstration of microglial activation in Alzheimer brain and in Alzheimer-related conditions opened the field of basic and applied investigations centered on the idea of a pathogenically important neuroinflammatory process in Alzheimer disease.