In vivo changes in microglial activation and amyloid deposits in brain regions with hypometabolism in Alzheimer's disease.
OBJECTIVE
Amyloid β protein (Aβ) is known as a pathological substance in Alzheimer's disease (AD) and is assumed to coexist with a degree of activated microglia in the brain. However, it remains unclear whether these two events occur in parallel with characteristic hypometabolism in AD in vivo. The purpose of the present study was to clarify the in vivo relationship between Aβ accumulation and neuroinflammation in those specific brain regions in early AD.


METHODS
Eleven nootropic drug-naïve AD patients underwent a series of positron emission tomography (PET) measurements with [(11)C](R)PK11195, [(11)C]PIB and [(18)F]FDG and a battery of cognitive tests within the same day. The binding potentials (BPs) of [(11)C](R)PK11195 were directly compared with those of [(11)C]PIB in the brain regions with reduced glucose metabolism.


RESULTS
BPs of [(11)C](R)PK11195 and [(11)C]PIB were significantly higher in the parietotemporal regions of AD patients than in ten healthy controls. In AD patients, there was a negative correlation between dementia score and [(11)C](R)PK11195 BPs, but not [(11)C]PIB, in the limbic, precuneus and prefrontal regions. Direct comparisons showed a significant negative correlation between [(11)C](R)PK11195 and [(11)C]PIB BPs in the posterior cingulate cortex (PCC) (p < 0.05, corrected) that manifested the most severe reduction in [(18)F]FDG uptake.


CONCLUSIONS
A lack of coupling between microglial activation and amyloid deposits may indicate that Aβ accumulation shown by [(11)C]PIB is not always the primary cause of microglial activation, but rather the negative correlation present in the PCC suggests that microglia can show higher activation during the production of Aβ in early AD.
Yokokura
Masamichi
M
Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Mori
Norio
N
Yagi
Shunsuke
S
Yoshikawa
Etsuji
E
Kikuchi
Mitsuru
M
Yoshihara
Yujiro
Y
Wakuda
Tomoyasu
T
Sugihara
Genichi
G
Takebayashi
Kiyokazu
K
Suda
Shiro
S
Iwata
Yasuhide
Y
Ueki
Takatoshi
T
Tsuchiya
Kenji J
KJ
Suzuki
Katsuaki
K
Nakamura
Kazuhiko
K
Ouchi
Yasuomi
Y
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D017628:Microglia / Q000378:metabolism*; D008875:Middle Aged; D009474:Neurons / Q000473:pathology; D049268:Positron-Emission Tomography; D011849:Radioactive Tracers
D016229:Amyloid beta-Peptides; D011849:Radioactive Tracers; D005947:Glucose