Concept & Aims


Microglia cells are the brain’s macrophages which are stimulated by and contribute to a variety of brain diseases. Reactive microglial cells derived from resident microglia have morphological features similar to infiltrated macrophages derived from bone marrow (BMDM), and they are involved in both, inflammation-mediated neurotoxicity as well as neuroregenerative repair mechanisms. The exact role, function and regulation of various microglia phenotypes still needs to be elucidated, but it is thought that microglial responsiveness to injury may serve as a valuable marker for early disease detection, progression, and outcome. It has been demonstrated that in 50% of patients with MCI microglial activation as depicted by PK11195-PET occurs in conjunction with detection of amyloid deposition as depicted by PIB-PET (Okello et al. 2009) suggesting that in vivo imaging of microglial reactivity may allow evaluation of disease progression, prediction of deterioration rate, and assessment of the effect of immunomodulatory therapies. Different activation patterns for peripheral macrophages and monocytes have been identified, e.g. M1-activated macrophages (M1) mediating TNF-β/iNOS expression and proteolytic activity, or M2-activated macrophages (M2) with immunomodulatory and tissue repair properties (Martinez et al. 2009). A subset of monocytes may constitute circulating precursors of microglia (Yong & Rivest 2009), and in experimental AD models it has been shown that BMDM may slow down disease progression by removing amyloid-β (Aβ) from the CNS (Simard et al. 2006). Therefore, the current view is that depending on the specific phenotype, microglia and macrophages may promote disease progression or serve in the process of Aβ plaque clearance, as being recently observed in immunization strategies with Aβ (Holmes et al. 2008) or bapineuzumab, an antibody targeted against Aβ resulting in a greater than 25% reduction of PIB-measured plaque load (Rinne et al. 2010). The main aim of this project is to increase the understanding of the regulation of microglial activity and function by imaging their dynamics in vivo to serve as biomarker of disease load and to follow immunomodulatory therapies.


The main aims of the INMiND project are:

  • to increase the understanding of the basic mechanisms of regulation of microglial activity and related functions by imaging their dynamics in vivo,
  • to employ activated microglia as a biomarker of NIND disease activity in animal model systems and patients with NIND (diagnosis),
  • to non-invasively follow the neuroprotective effects of immunomodulatory therapies in patients with MCI in vivo in order to preserve neuronal function as early as possible in the disease course. With that, we aim to identify molecular target / imaging biomarker combinations which can be used for early diagnosis, assessment of disease activity and therapy (theranostics). We expect that knowledge and paradigms generated by the INMiND project will be translatable to the development of therapeutic paradigms for a broad range of NINDs.

To reach these aims the INMiND consortium will:

  • investigate the concerted action of protein-deposition and inflammatory response on the neurodegenerative and neuroregenerative processes, not only at the cellular level but also in the living system (animal model, patient),
  • investigate the role of microglial activation on the disease process (early diagnosis, activity, response to therapy) employing improved and innovative imaging technologies which will allow for assessment of the dynamics of microglial activity in vivo over time,
  • investigate genetic and pharmacological strategies to modulate inflammatory responses favouring neuroprotection and neuroregeneration,
  • develop disease markers for early diagnosis to allow for application of neuroprotective/immunomodulatory strategies that are aimed at preventing inflammation-induced neuronal death as early as possible in the disease course.

INMiND Office
European Institute for Molecular Imaging (EIMI) Waldeyerstr. 15
· 48149 Münster
Tel: +49 251 83 49300 · Fax: +49 251 83 49313