In vivo detection of microglia activation in frontotemporal dementia

MRC Cyclotron Unit, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus, London, United Kingdom.
Annals of Neurology (Impact Factor: 9.98). 12/2004; 56(6):894-7. DOI: 10.1002/ana.20332
Source: PubMed


Using positron emission tomography and [(11)C](R)-PK11195, a marker of "peripheral benzodiazepine sites" that is upregulated on activated microglia during progressive tissue pathology, we show increased binding of [(11)C](R)-PK11195 in frontotemporal lobar degeneration in the typically affected frontotemporal brain regions. This implies the presence of an active glial response reflecting progressive neuronal degeneration. It also suggests that increased [(11)C](R)-PK11195 binding, previously demonstrated for Alzheimer's disease, may occur independently from increased amyloid plaque formation, given that it is not a characteristic feature of frontotemporal lobar degeneration.


Available from: Elizabeth L Sampson, Mar 23, 2015
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    • "We find a highly significant correlation between plasma PGRN and IL-6 levels in patients with FTLD, but not in AD or control subjects. This finding in FTLD is perhaps not surprising given that PGRN expression is driven by IL-6 secretion (Frampton et al., 2012), perhaps reflecting increased microglial activity especially in GRN carriers (Ahmed et al., 2007; Cagnin et al., 2004) or in normal control subjects. However, if so, it is curious as to why a similar association is not seen in AD where senile plaques are heavily invested with microglial cells. "
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    ABSTRACT: We have measured plasma progranulin and interleukin-6 in 230 patients with frontotemporal lobar degeneration (FTLD), 104 patients with Alzheimer's disease, and 161 control subjects. We have replicated previous findings of decreased levels of progranulin protein in FTLD because of mutations in GRN and show this is not observed in FTLD cases because of other causes. interleukin-6 levels were increased in FTLD overall, but these did not discriminate between clinical and genetic subtypes. Copyright © 2014 Elsevier Inc. All rights reserved.
    Neurobiology of Aging 10/2014; 36(3). DOI:10.1016/j.neurobiolaging.2014.10.023 · 5.01 Impact Factor
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    • "Cagnin et al. [118] first observed microglial activation in FTLD. They used positron emission tomography and a marker of “peripheral benzodiazepine sites,” [11C] (R)-PK11195, which is upregulated on activated microglia during progressive tissue pathology [119]. "
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    ABSTRACT: In the last few years, genetic and biomolecular mechanisms at the basis of Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) have been unraveled. A key role is played by microglia, which represent the immune effector cells in the central nervous system (CNS). They are extremely sensitive to the environmental changes in the brain and are activated in response to several pathologic events within the CNS, including altered neuronal function, infection, injury, and inflammation. While short-term microglial activity has generally a neuroprotective role, chronic activation has been implicated in the pathogenesis of neurodegenerative disorders, including AD and FTLD. In this framework, the purpose of this review is to give an overview of clinical features, genetics, and novel discoveries on biomolecular pathogenic mechanisms at the basis of these two neurodegenerative diseases and to outline current evidence regarding the role played by activated microglia in their pathogenesis.
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    • "The main role of TSPO is the transportation of cholesterol across the outer mitochondria membrane, the rate limiting step of steroidogenesis . Upregulation of TSPO is seen in many CNS diseases, including Alzheimer's, (Edison, 2008; Yasuno, 2008) Huntington's, (Meßmer & Reynolds, 1998) brain tumours, (Vlodavsky & Soustiel, 2007) traumatic brain injury, (Papadopoulos & Lecanu, 2009) ischaemic stroke, (Cosenza-Nashat, 2009; Gerhard, 2005) frontotemporal dementia, (Cagnin, 2004) amyotrophic lateral sclerosis, (Turner, 2004) Parkinson's (Ouchi, 2005) and multiple sclerosis (MS) (Versijpt, 2005; Vowinckel, 1997). The prevalence of TSPO in CNS disorders has given credence to the targeting of TSPO as a possible disease modifier. "
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