The microglia comprise 20% of white cells and when activated by disease provide the natural immune defence of the brain. All neurodegenerative disorders are associated with microglial activation but the role of these cells in driving disease or protecting against the presence of pathology is still uncertain. When activated, microglia express the translocator protein (TSPO) which transports nutrients and modulates the membrane potential of mitochondria. PET ligands are now available that bind to TSPO allowing the distribution and time course of microglial activation to be imaged in vivo. In this lecture the spatial and temporal patterns of microglial activation in dementias and Parkinsonian syndromes will be illustrated and their relationship to clinical status will be discussed. It will be suggested that microglial activation may occur in tow phases – an initial protective phase which fails followed by a second tidal phase that acts to drive disease. Effective and non‑toxic treatments which stimulate the first phase but suppress the second phase need to be further developed. FINANCIAL SUPPORT: Medical research Council UK, Alzheimer Research UK, Danish Council for Independent Research, Lundbeck Foundation.
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