Glia and their cytokines in progression of neurodegeneration

A glia-mediated, inflammatory immune response is an important component of the neuropathophysiology of Alzheimerʹs disease, of the midlife neurodegeneration of Downʹs syndrome, and of other age-related neurodegenerative conditions. All of these conditions are associated with early and often dramatic activation of, and cytokine overexpression in, microglia and astrocytes, sometimes decades before pathological changes consistent with a diagnosis of Alzheimerʹs disease are apparent, as in patients with Downʹs syndrome or head injury. Brains of normal elderly individuals also often show Alzheimer-type neuropathological changes, although to a lesser degree than those seen in Alzheimerʹs disease itself. These normal age-related glial changes, likely a response to the normal wear and tear of the aging process, raise the threshold of glial activation and thus may explain the fact that even genetically determined Alzheimerʹs disease, resulting from genetic mutations such as those in β-amyloid precursor protein and presenilins or from genetic duplication such as of chromosome 21, only shows the full manifestation of the disease decades after birth. In the more common sporadic form of Alzheimerʹs disease, age-related increases in glial activation and expression of cytokines may act in synergy with other genetic and acquired environmental risks to culminate in the development of disease.