Assessment of neuroinflammation and microglial activation in Alzheimer's disease with radiolabelled PK11195 and single photon emission computed tomography. A pilot study.
OBJECTIVE
Inflammation contributes to degeneration in Alzheimer's disease (AD), not simply as a secondary phenomenon, but primarily as a significant source of pathology. [(123)I]iodo-PK11195 is a single photon emission computed tomography (SPECT) ligand for the peripheral benzodiazepine receptor, the latter being expressed on microglia (brain resident macrophages) and upregulated under inflammatory circumstances. The objectives were to assess AD inflammation by detecting [(123)I]iodo-PK11195 uptake changes and investigate how uptake values relate with perfusion SPECT and neuropsychological findings.


METHODS
Ten AD and 9 control subjects were included. [(123)I]iodo-PK11195 SPECT images were realigned into stereotactic space where binding indices, normalized on cerebellar uptake, were calculated.


RESULTS
The mean [(123)I]iodo-PK11195 uptake was increased in AD patients compared with controls in nearly all neocortical regions; however, statistical significance was only reached in the frontal and right mesotemporal regions. Significant correlations were found between regional increased [(123)I]iodo-PK11195 uptake and cognitive deficits.


CONCLUSIONS
[(123)I]iodo-PK11195 is a cellular disease activity marker and allows in vivo assessment of microglial inflammation in AD.
Versijpt
Jan J
JJ
Department of Biological Psychiatry, University Hospital Groningen, Groningen, The Netherlands. jan.versijpt@rug.ac.be
Dumont
Filip
F
Van Laere
Koen J
KJ
Decoo
Danny
D
Santens
Patrick
P
Audenaert
Kurt
K
Achten
Eric
E
Slegers
Guido
G
Dierckx
Rudi A
RA
Korf
Jakob
J
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000276:immunology / Q000473:pathology; D001931:Brain Mapping; D004292:Dominance, Cerebral / Q000502:physiology; D004660:Encephalitis / Q000000981:diagnostic imaging* / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007457:Iodine Radioisotopes; D007546:Isoquinolines; D008297:Male; D008609:Mental Status Schedule; D017628:Microglia / Q000000981:diagnostic imaging* / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D019579:Neocortex / Q000000981:diagnostic imaging* / Q000276:immunology / Q000473:pathology; D010865:Pilot Projects; D011869:Radioligand Assay; D011963:Receptors, GABA-A / Q000502:physiology*; D012016:Reference Values; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D015854:Up-Regulation / Q000502:physiology
D007457:Iodine Radioisotopes; D007546:Isoquinolines; D011963:Receptors, GABA-A; C037850:PK 11195