Microglial activation in healthy aging

Schuitemaker, Alie; Doef, Thalia F. van der; Boellaard, Ronald; Flier, Wiesje M. van der; Yaqub, Maqsood; Windhorst, Albert D.; Barkhof, Frederik; Jonker, Cees; Kloet, Reina W.; Lammertsma, Adriaan A.; Scheltens, Philip; Berckel, Bart N.M. van

doi:10.1016/j.neurobiolaging.2010.09.016

Cited by 123 publications

(90 citation statements)

References 28 publications

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“…Five of the 7 MCI subjects who were followed for 5 years eventually developed AD and 1 was diagnosed with Lewy body disease [67]. Schuitemaker et al [128] studied [ 11 C]PK-11195 binding in 10 MCI subjects and compared them with 19 AD patients and 21 healthy controls. They reported increased binding in the occipital lobe in AD compared to controls, but no difference in PK-11195 binding between clinically stable MCI subjects and those who progressed to dementia.…”

Section: Resultsmentioning

confidence: 99%

“…The overall pattern of [ 11 C]PK-11195 distribution in the brain was the same in the adults and in the children, although the intensity of uptake was increased in specific regions such as the midbrain and thalamus, contrasting with a lower uptake in the frontal, parietal and temporal cortex [163]. More recently, Schuitemaker et al [128] reported an increase in the specific binding of [ 11 C]PK-11195 with aging in healthy subjects (19-79 years old) in several cortical and subcortical areas (frontal cortex, anterior and posterior cingulate cortex, medial inferior temporal lobe, insula, hippocampus, entorhinal cortex, thalamus, parietal and occipital cortex and cerebellum) [128]. Gulyas et al [164] used PET with [ 11 C]vinpocetine, another TSPO radioligand, to study microglial activation during normal brain aging (healthy volunteers aged between 25 and 78 years) and reported increased uptake and binding with age in the entire brain and in all the brain regions studied.…”

Section: Discussionmentioning

confidence: 99%

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Neuroinflammation and β Amyloid Deposition in Alzheimer's Disease: In vivo Quantification with Molecular Imaging

Hommet

Mondon²,

Camus³

et al. 2013

Dement Geriatr Cogn Disord

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Background/Aims: Neuroinflammation plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Its relationship with underlying β amyloid deposition remains unclear. In vivo visualization of microglial activation has become possible with the development of molecular imaging ligands when used with positron emission tomography (PET). The translocator protein (TSPO) is upregulated during neuroinflammation. Consequently, targeting TSPO with radiolabeled ligands for PET is an attractive biomarker for neuroinflammation. Methods: A review of the research literature on PET imaging which studied in vivo neuroinflammation in AD subjects and its relationship with amyloid load was performed, including papers published between 2001 and 2012. Results: Six studies were included using either [¹¹C]PK-11195 or another non-TSPO radioligand that binds to the monoaminooxidase B. All the studies evaluated amyloid load with [¹¹C]PIB. Microglial activation and astrocytosis are potentially early phenomena in AD. However, the individual levels of amyloid deposition and microglial activation were not correlated. Conclusion: Noninvasive in vivo molecular imaging to visualize neuroinflammation in AD may contribute to our understanding of the kinetics of neuroinflammation and its relationship to the hallmarks of the disease. Both are important for the development of future therapeutic modalities and for quantifying the efficacy of future disease-modifying treatments.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Neuroinflammation and β Amyloid Deposition in Alzheimer's Disease: In vivo Quantification with Molecular Imaging

Hommet

Mondon²,

Camus³

et al. 2013

Dement Geriatr Cogn Disord

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show abstract

“…The increasing amount of altered macromolecules and release of signal molecules from ageing damaged neurons activate the immune system of the brain [116,117]. The major cell types of the immune system in the brain are astrocytes and microglial cells.…”

Section: Processes Contributing To Brain Ageingmentioning

confidence: 99%

The endocannabinoid system in normal and pathological brain ageing

Bilkei-Gorzó

2012

Phil. Trans. R. Soc. B

121

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The role of endocannabinoids as inhibitory retrograde transmitters is now widely known and intensively studied. However, endocannabinoids also influence neuronal activity by exerting neuroprotective effects and regulating glial responses. This review centres around this less-studied area, focusing on the cellular and molecular mechanisms underlying the protective effect of the cannabinoid system in brain ageing. The progression of ageing is largely determined by the balance between detrimental, proageing, largely stochastic processes, and the activity of the homeostatic defence system. Experimental evidence suggests that the cannabinoid system is part of the latter system. Cannabinoids as regulators of mitochondrial activity, as anti-oxidants and as modulators of clearance processes protect neurons on the molecular level. On the cellular level, the cannabinoid system regulates the expression of brainderived neurotrophic factor and neurogenesis. Neuroinflammatory processes contributing to the progression of normal brain ageing and to the pathogenesis of neurodegenerative diseases are suppressed by cannabinoids, suggesting that they may also influence the ageing process on the system level. In good agreement with the hypothesized beneficial role of cannabinoid system activity against brain ageing, it was shown that animals lacking CB1 receptors show early onset of learning deficits associated with age-related histological and molecular changes. In preclinical models of neurodegenerative disorders, cannabinoids show beneficial effects, but the clinical evidence regarding their efficacy as therapeutic tools is either inconclusive or still missing.

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“…The concentration of classical complement cascade C1q subunit decreases in CSF of AD patients and is correlated with disease severity (Smyth, Cribbs et al 1994). However, this intrathecal molecule only attests for microglial reactions met in AD and also during physiological aging (Lue, Walker et al 2001;Schuitemaker, van der Doef et al 2011). Similarly isoprostane CSF levels, an oxidative stress marker, clearly increase in biological fluid (CSF, blood and urine) proportionally to cognitive decline and might be an early biomarker of AD in MCI patients (Pratico, Clark et al 2000;Pratico, Clark et al 2002).…”

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confidence: 99%