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Clayton A. Wiley, MD, PhD; Brian J. Lopresti, BS; Sriram Venneti, MD, PhD; Julie Price, PhD; William E. Klunk, MD, PhD; Steven T. DeKosky, MD; Chester A. Mathis, PhD

Arch Neurol. 2009;66(1):60-67.

Background  Alzheimer disease (AD) is defined neuropathologically by the presence of neurofibrillary tangles and plaques associated with tau and β-amyloid protein deposition. The colocalization of microglia and β-amyloid plaques has been widely reported in pathological examination of AD and suggests that neuroinflammation may play a role in pathogenesis and/or progression. Because postmortem histopathological analyses are limited to single end-stage assessment, the time course and nature of this relationship are not well understood.

Objective  To image microglial activation and β-amyloid deposition in the brains of subjects with and without AD.

Design, Setting, and Participants  Using two carbon 11 ([¹¹C])–labeled positron emission tomographic imaging agents, Pittsburgh Compound B (PiB) and (R)-PK11195, we examined the relationship between amyloid deposition and microglial activation in different stages of AD using 5 control subjects, 6 subjects diagnosed with mild cognitive impairment, and 6 patients with mild to moderate AD.

Results  Consistent with prior reports, subjects with a clinical diagnosis of probable AD showed significantly greater levels of [¹¹C]PiB retention than control subjects, whereas patients with mild cognitive impairment spanned a range from control-like to AD-like levels of [¹¹C]PiB retention. Additionally, 2 asymptomatic control subjects also exhibited evidence of elevated PiB retention in regions associated with the early emergence of plaques in AD and may represent prodromal cases of AD. We observed no differences in brain [¹¹C](R)-PK11195 retention when subjects were grouped by clinical diagnosis or the presence or absence of β-amyloid pathological findings as indicated by analyses of [¹¹C]PiB retention.

Conclusions  These findings suggest that either microglial activation is limited to later stages of severe AD or [¹¹C](R)-PK11195 is too insensitive to detect the level of microglial activation associated with mild to moderate AD.

Author Affiliations: Departments of Pathology (Drs Wiley and Venneti), Radiology (Mr Lopresti and Drs Price and Mathis), Psychiatry (Dr Klunk), and Neurology (Dr DeKosky), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Dr Venneti is now with the Department of Pathology, University of Pennsylvania, Philadelphia.

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