Early and progressive accumulation of reactive microglia in the Huntingtondisease brain

Microglia may contribute to cell death in neurodegenerative diseases. We st udied the activation of microglia in affected regions of Huntington disease (HD) brain by localizing thymosin beta -4 (T beta4), which is increased in reactive microglia. Activated microglia appeared in the neostriatum, corte x, and globus pallidus and the adjoining white matter of the HD brain, but not in control brain. In the striatum and cortex, reactive microglia occurr ed in all grades of pathology, accumulated with increasing grade, and grew in density in relation to degree of neuronal loss. The predominant morpholo gy of activated microglia differed in the striatum and cortex. Processes of reactive microglia were conspicuous in low-grade HD, suggesting an early m icroglia response to changes in neuropil and axons and in the grade 2 and g rade 3 cortex, were aligned with the apical dendrites of pyramidal neurons. Some reactive microglia contacted pyramidal neurons with huntingtin-positi ve nuclear inclusions. The early and proximate association of activated mic roglia with degenerating neurons in the HD brain implicates a role for acti vated microglia in HD pathogenesis.