In-vivo measurement of activated microglia in dementia

• Published in: The Lancet (British edition) 2001-08, Vol.358 (9280), p.461-467
• Main Authors: Cagnin, Annachiara, Brooks, David J, Kennedy, Angus M, Gunn, Roger N, Myers, R, Turkheimer, Federico E, Jones, Terry, Banati, Richard B
• Format: Article
• Language: English
• Subjects: Activation; Adult; Age; Aged; Aged, 80 and over; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - etiology; Alzheimer Disease - pathology; Alzheimer's disease; Atrophy; Benzodiazepines; Binding sites; Brain; Brain - diagnostic imaging; Brain - metabolism; Brain - pathology; Brain research; Carbon Radioisotopes; Case-Control Studies; Cluster analysis; Cognitive ability; Cortex (cingulate); Cortex (entorhinal); Degeneration; Dementia; Dementia disorders; Female; Humans; Immune response; Immune system; Inflammation - pathology; Isoquinolines; Ligands; Magnetic Resonance Imaging; Male; Medical diagnosis; Medical research; Medical screening; Memory; Microglia; Microglia - pathology; Middle Aged; Neurodegeneration; Neurodegenerative diseases; Neuroimaging; Neurosciences; NMR; Nuclear magnetic resonance; Pathogenesis; Patients; Positron emission; Positron emission tomography; Receptors; Receptors, GABA-A - metabolism; Thalamus; Tomography; Tomography, Emission-Computed
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(01)05625-2

Background Activated microglia have a key role in the brain's immune response to neuronal degeneration. The transition of microglia from the normal resting state to the activated state is associated with an increased expression 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. 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 specific ligand for the peripheral benzodiazepine binding site. In normal individuals, regional [11C](R)-PK11195 binding did not significantly change with age, except in the thalamus, where an age-dependent increase was found. By contrast, patients with Alzheimer's disease showed significantly increased regional [11C](R)-PK11195 binding in the entorhinal, temporoparietal, and cingulate cortex. In-vivo detection of increased [11C](R)-PK11195 binding in Alzheimer-type dementia, including mild and early forms, suggests that microglial activation is an early event in the pathogenesis of the disease.