RT Journal Article
SR Electronic
T1 Microglial activation and amyloid deposition in mild cognitive impairment
JF Neurology
JO Neurology
FD Lippincott Williams & Wilkins
SP 56
OP 62
DO 10.1212/01.wnl.0000338622.27876.0d
VO 72
IS 1
A1 Okello, A.
A1 Edison, P.
A1 Archer, H. A.
A1 Turkheimer, F. E.
A1 Kennedy, J.
A1 Bullock, R.
A1 Walker, Z.
A1 Kennedy, A.
A1 Fox, N.
A1 Rossor, M.
A1 Brooks, D. J.
YR 2009
UL http://n.neurology.org/content/72/1/56.abstract
AB Background: Activated microglia may play a role in the pathogenesis of Alzheimer disease (AD) as they cluster around beta-amyloid (Aβ) plaques. They are, therefore, a potential therapeutic target in both AD and its prodrome amnestic mild cognitive impairment (MCI). Objective: To characterize in vivo with 11C-(R)-PK11195 and 11C-PIB PET the distribution of microglial activation and amyloid deposition in patients with amnestic MCI. Methods: Fourteen subjects with MCI had 11C-(R)-PK11195 and 11C-PIB PET with psychometric tests. Results: Seven out of 14 (50%) patients with MCI had increased cortical 11C-PIB retention (p < 0.001) while 5 out of 13 (38%) subjects with MCI showed increased 11C-(R)-PK11195 uptake. The MCI subgroup with increased 11C-PIB retention also showed increased cortical 11C-(R)-PK11195 binding (p < 0.036) though this increase only remained significant in frontal cortex after a correction for multiple comparisons. There was no correlation between regional levels of 11C-(R)-PK11195 and 11C-PIB binding in individual patients with MCI: only three of the five MCI cases with increased 11C-(R)-PK11195 binding had increased levels of 11C-PIB retention. Conclusions: Our findings indicate that, while amyloid deposition and microglial activation can be detected in vivo in around 50% of patients with mild cognitive impairment (MCI), these pathologies can occur independently. The detection of microglial activation in patients with MCI suggests that anti-inflammatory therapies may be relevant to the prevention of AD. Aβ=beta-amyloid; AD=Alzheimer disease; BP=binding potential; MCI=mild cognitive impairment; MMSE=Mini-Mental State Examination; PBBS=peripheral benzodiazepine binding site; ROI=region of interest; SD=standard deviation; SRTM=simplified reference tissue model.