In-vivo measurement of activated microglia in dementia

Annachiara Cagnin, David J. Brooks, Angus M. Kennedy, Roger N. Gunn, R. Myers, Federico E. Turkheimer, Terry Jones, Richard B. Banati

Research output: Contribution to journalArticle

774 Citations (Scopus)

Abstract

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. 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 specific ligand for the peripheral benzodiazepine binding site. Findings 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. Interpretation 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.

Original languageEnglish
Pages (from-to)461-467
Number of pages7
JournalLancet
Volume358
Issue number9280
DOIs
Publication statusPublished - Aug 11 2001

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Microglia
Dementia
Alzheimer Disease
Benzodiazepines
Binding Sites
Entorhinal Cortex
Gyrus Cinguli
Phagocytes
Thalamus
Neuroimaging
Neuroglia
Positron-Emission Tomography
Carbon
Ligands
Brain
(R)-(11C)1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Cagnin, A., Brooks, D. J., Kennedy, A. M., Gunn, R. N., Myers, R., Turkheimer, F. E., ... Banati, R. B. (2001). In-vivo measurement of activated microglia in dementia. Lancet, 358(9280), 461-467. https://doi.org/10.1016/S0140-6736(01)05625-2

In-vivo measurement of activated microglia in dementia. / Cagnin, Annachiara; Brooks, David J.; Kennedy, Angus M.; Gunn, Roger N.; Myers, R.; Turkheimer, Federico E.; Jones, Terry; Banati, Richard B.

In: Lancet, Vol. 358, No. 9280, 11.08.2001, p. 461-467.

Research output: Contribution to journalArticle

Cagnin, A, Brooks, DJ, Kennedy, AM, Gunn, RN, Myers, R, Turkheimer, FE, Jones, T & Banati, RB 2001, 'In-vivo measurement of activated microglia in dementia', Lancet, vol. 358, no. 9280, pp. 461-467. https://doi.org/10.1016/S0140-6736(01)05625-2
Cagnin A, Brooks DJ, Kennedy AM, Gunn RN, Myers R, Turkheimer FE et al. In-vivo measurement of activated microglia in dementia. Lancet. 2001 Aug 11;358(9280):461-467. https://doi.org/10.1016/S0140-6736(01)05625-2
Cagnin, Annachiara ; Brooks, David J. ; Kennedy, Angus M. ; Gunn, Roger N. ; Myers, R. ; Turkheimer, Federico E. ; Jones, Terry ; Banati, Richard B. / In-vivo measurement of activated microglia in dementia. In: Lancet. 2001 ; Vol. 358, No. 9280. pp. 461-467.
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