In-vivo measurement of activated microglia in dementia

Background Activated microglia have a key role in the brain's immune respon se to neuronal degeneration. The transition of microglia from the normal re sting state to the activated state is associated with an increased expressi on of receptors known as peripheral benzodiazepine binding sites, which are abundant on cells of mononuclear phagocyte lineage. We used brain imaging to study expression of these sites in healthy individuals and patients with Alzheimer's disease. Methods We studied 15 normal individuals (age 32-80 years), eight patients with Alzheimer's disease, and one patient with minimal cognitive impairment . Quantitative in-vivo measurements of glial activation were obtained with positron emission tomography (PET) and carbon-11-labelled (R)-PK11195, a sp ecific ligand for the peripheral benzodiazepine binding site. Findings In normal individuals, regional [C-11](R)-PK11195 binding did not significantly change with age, except in the thalamus, where an age-depende nt increase was found. By contrast, patients with Alzheimer's disease showe d significantly increased regional [C-11](R)-PK11195 binding in the entorhi nal, temporoparietal, and cingulate cortex. Interpretation In-vivo detection of increased [C-11](R)-PK11195 binding in Alzheimer-type dementia, including mild and early forms, suggests that micr oglial activation is an early event in the pathogenesis of the disease.