Microglial activation in healthy aging.
Healthy brain aging is characterized by neuronal loss and decline of cognitive function. Neuronal loss is closely associated with microglial activation and postmortem studies have indeed suggested that activated microglia may be present in the aging brain. Microglial activation can be quantified in vivo using (R)-[(11)C]PK11195 and positron emission tomography. The purpose of this study was to measure specific binding of (R)-[(11)C]PK11195 in healthy subjects over a wide age range. Thirty-five healthy subjects (age range 19-79 years) were included. In all subjects 60-minute dynamic (R)-[(11)C]PK11195 scans were acquired. Specific binding of (R)-[(11)C]PK11195 was calculated using receptor parametric mapping in combination with supervised cluster analysis to extract the reference tissue input function. Increased binding of (R)-[(11)C]PK11195 with aging was found in frontal lobe, anterior and posterior cingulate cortex, medial inferior temporal lobe, insula, hippocampus, entorhinal cortex, thalamus, parietal and occipital lobes, and cerebellum. This indicates that activated microglia appear in several cortical and subcortical areas during healthy aging, suggesting widespread neuronal loss.
Department of Neurology and Alzheimer Centre, VU University Medical Centre, Amsterdam, the Netherlands. a.schuitemaker@vumc.nl
Alie
A
Schuitemaker
Thalia F
TF
van der Doef
Ronald
R
Boellaard
Wiesje M
WM
van der Flier
Maqsood
M
Yaqub
Albert D
AD
Windhorst
Frederik
F
Barkhof
Cees
C
Jonker
Reina W
RW
Kloet
Adriaan A
AA
Lammertsma
Philip
P
Scheltens
Bart N M
BN
van Berckel
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D001921:Brain / Q000166:cytology* / Q000378:metabolism*; D016922:Cellular Senescence / Q000502:physiology*; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000166:cytology / Q000378:metabolism*; D008875:Middle Aged; D011485:Protein Binding / Q000502:physiology; D055815:Young Adult
D007546:Isoquinolines; C037850:PK 11195