Fig. 3

Collateral neuronal damage is clearly inherent to primary neuroinflammatory diseases, and neuroinflammation is a likely consequence of primary neurodegeneration. a In primary degenerative diseases like AD and in stroke, a non-immune-mediated CNS injury is initiated. Immune response cells, predominantly local microglia, marcophages and lymphocytes, are involved in the degenerative processes and elicit a secondary inflammatory reaction, which sets the pace of progressive neuronal damage. Some of these mechanisms might also occur at certain stages of MS. b In primary inflammatory CNS disease such as MS, activated immune cells—namely, microglia, macrophages and lymphocytes—attack a common target antigen of the brain, typically part of the myelin sheath. Demyelination, axonal transection and neuronal death can occur during the immune response. The loss of myelin might result in secondary axonal transection (outside-in damage) or, vice versa, death of an axon can lead to secondary demyelination (inside-out damage). Some of these sequences constitute the pathogenesis of diseases like AD