Glial Activation as a Common Denominator in Neurodegenerative Disease: A Hypothesis in Neuropathophysiology

Abstract

The presence of large numbers of activated microglia and astroglia (gliosis) is a hallmark of neurodegeneration. However, neither the molecular impetus for glial activation in neurodegeneration nor its consequences are understood. Glial proliferation and hypertrophy may be found in diverse neurodegenerative conditions: vascular insufficiency, as in stroke (Garcia, 1992); trauma, as in dementia pugilistica (Corsellis et al., 1973) and experimentally induced central nervous system (CNS) lesions (Rio-Hortega and Penfield, 1927; Cavanaugh, 1970; Bigmami and Dahl, 1976; Latov et al., 1979); exposure to infectious agents, as in AIDS (Navia et al., 1986; Budka et al., 1987; Wiley et al., 1991) and scrapie (Diedrich et al., 1991); genetic defects, as in trisomy 21 (Down’s syndrome) (Meyer et al., 1939; Wisniewski et al., 1985; Griffin et al., 1989) and familial Alzheimer’s disease (Murphy and Ellis, 1991); and unknown agents, as in sporadic Alzheimer’s disease (Schechter et al., 1981; Mancardi et al., 1983; Griffin et al., 1989; Delacourte, 1990; Mandybur and Chuirazzi, 1990; Diedrich et al., 1991; Frederickson, 1992). Although gliosis is the common thread in these neurodegenerative diseases, most studies have focused on other neuropathophysiological features. For example, the severe gliosis that accompanies the neuronal and extracellular alterations in dementia pugilistica has been recognized for some time (Corsellis et al., 1973), but the distribution of activated glia and glia-derived cytokines in this disorder is only now under investigation (G.W. Roberts, personal communication).