Activated MAO-B in the brain of Alzheimer patients, demonstrated by [11C]-l-deprenyl using whole hemisphere autoradiography

Gulyás, Balázs; Pavlova, Elena; Kása, P.; Gulya, Károly; Bakota, Lidia; Varszegi, Szilvia; Keller, Éva; Horvath, M.C.; Nag, Sangram; Hermecz, István; Magyar, K.; Halldin, Christer

doi:10.1016/j.neuint.2010.10.013

Cited by 182 publications

(226 citation statements)

References 66 publications

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“…This was demonstrated by [ 11 C]-L-deprenyl using whole hemisphere autoradiography (38)(39)(40), epidemiology (41,42), morphology (43), as well as single-photon emission computed tomography (44). Such studies demonstrated that: i) MAO activity in platelets was significantly increased in patients with AD and acted as a marker of behavioral characteristics in dementia disorders (41,(45)(46)(47)(48); ii) there were early and persistent alterations in MAO-A and -B in the brains of patients with AD (49); iii) activated MAO led to cognitive dysfunction (50); iv) activated MAO destroyed cholinergic neurons and caused disorders of the cholinergic system (51); v) activated MAO contributed to the formation of amyloid plaques (13,14) and vi) activated MAO was associated with the formation of NFTs.…”

Section: Involvement Of Mao In Neurodegenerationmentioning

confidence: 95%

“…Furthermore, oxidative stress and neuroinflammation are critical in the pathogenic cascade of neurodegeneration in AD, suggesting that therapeutic efforts aimed at these two mechanisms may be beneficial. It has been evidenced that several MAO inhibitors restrain the production of Aβ by inhibiting neuroinflammation, such as the inhibition of nuclear factor κB activity, the downregulation of the expression of interleukin 1β and tumor necrosis factor α, and the limitation of glial activation (38,128,129).…”

Section: Activated Mao Contributes To the Formation Of Amyloid Plaquesmentioning

confidence: 99%

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Monoamine oxidase inhibitors: Promising therapeutic agents for Alzheimer’s disease (Review)

Cai

2014

Molecular Medicine Reports

180

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Abstract. Activated monoamine oxidase (MAO) has a critical role in the pathogenesis of Alzheimer's disease (AD), including the formation of amyloid plaques from amyloid β peptide (Aβ) production and accumulation, formation of neurofibrillary tangles, and cognitive impairment via the destruction of cholinergic neurons and disorder of the cholinergic system. Several studies have indicated that MAO inhibitors improve cognitive deficits and reverse Aβ pathology by modulating proteolytic cleavage of amyloid precursor protein and decreasing Aβ protein fragments. Thus, MAO inhibitors may be considered as promising therapeutic agents for AD.

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Section: Involvement Of Mao In Neurodegenerationmentioning

confidence: 95%

Section: Activated Mao Contributes To the Formation Of Amyloid Plaquesmentioning

confidence: 99%

Monoamine oxidase inhibitors: Promising therapeutic agents for Alzheimer’s disease (Review)

Cai

2014

Molecular Medicine Reports

180

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“…The enzyme is overexpressed in reactive astrocytes, such as those for example in AD. Several clinical PET studies have thus suggested that [ 11 C]DED can be used as a PET ligand for measuring the MAO-B activity in AD brains as an in vivo marker for early disease progression [25][26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Astroglial Responses to Amyloid-Beta Progression in a Mouse Model of Alzheimer’s Disease

et al. 2018

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Purpose: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloidbeta (Aβ) deposition, hyperphosphorylation of tau, and neuroinflammation. Astrocytes, the most abundant glial cell type in the nervous system, respond to neurodegenerative disorders through astrogliosis, i.e., converting to a reactive inflammatory state. The aim of this study was to investigate how in vivo quantification of astrogliosis using positron emission tomography (PET) radioligand deuterium-L-[ 11 C]deprenyl ([ 11 C]DED), binding to enzyme monoamine oxidase-B (MAO-B) which is overexpressed in reactive astrocytes during AD, corresponds to expression of glial fibrillary acidic protein (GFAP) and vimentin, i.e., two well-established markers of astrogliosis, during Aβ pathology progression. Procedures: APP ArcSwe mice (n = 37) and wild-type (WT) control mice (n = 23), 2-16-month old, were used to investigate biomarkers of astrogliosis. The radioligand, [ 11 C]DED, was used as an in vivo marker while GFAP, vimentin, and MAO-B were used to investigate astrogliosis and macrophage-associated lectin (Mac-2) to investigate microglia/macrophage activation by immunohistochemistry of the mouse brain. Aβ and GFAP levels were also measured with ELISA in brain homogenates. Results: The intrabrain levels of aggregated Aβ and reactive astrocytes were found to be elevated in APP ArcSwe compared with WT mice. GFAP and vimentin expression increased with age, i.e., with Aβ pathology, in the APP ArcSwe mice. This was not the case for in vivo marker [ 11 C]DED that showed elevated binding of the same magnitude in APP ArcSwe mice compared with WT mice at both 8 and 16 months. Further, immunohistochemistry indicated that there was limited co-expression of MAO-B and GFAP. Conclusions: MAO-B levels are increased early in Aβ pathology progression, while GFAP and vimentin appear to increase later, most likely as a consequence of abundant Aβ plaque formation. Thus, [ 11 C]DED is a useful PET radioligand for the detection of changes in MAO-B at an early stage of Electronic supplementary material The online version of this article (https:// doi.org/10.1007/s11307-017-1153-z) contains supplementary material, which is available to authorized users.Correspondence to: Stina Syvänen; e-mail: stina.syvanen@pubcare.uu.se AD progression but does not measure the total extent of astrogliosis at advanced stages of Aβ pathology.

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“…A recent autoradiography study (20) suggested 11 C-DED as a suitable in vivo PET ligand for assessing MAO-B in AD brains. This study demonstrated greater binding in the temporal lobe and white matter of AD brains compared with controls.…”

mentioning

confidence: 99%

Evidence for Astrocytosis in Prodromal Alzheimer Disease Provided by ¹¹C-Deuterium-L-Deprenyl: A Multitracer PET Paradigm Combining ¹¹C-Pittsburgh Compound B and ¹⁸F-FDG

Carter

Schöll²,

Almkvist³

et al. 2012

J Nucl Med

383

312

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Activated MAO-B in the brain of Alzheimer patients, demonstrated by [11C]-l-deprenyl using whole hemisphere autoradiography

Cited by 182 publications

References 66 publications

Monoamine oxidase inhibitors: Promising therapeutic agents for Alzheimer’s disease (Review)

Monoamine oxidase inhibitors: Promising therapeutic agents for Alzheimer’s disease (Review)

Astroglial Responses to Amyloid-Beta Progression in a Mouse Model of Alzheimer’s Disease

Evidence for Astrocytosis in Prodromal Alzheimer Disease Provided by ¹¹C-Deuterium-L-Deprenyl: A Multitracer PET Paradigm Combining ¹¹C-Pittsburgh Compound B and ¹⁸F-FDG

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Activated MAO-B in the brain of Alzheimer patients, demonstrated by [11C]-l-deprenyl using whole hemisphere autoradiography

Cited by 182 publications

References 66 publications

Monoamine oxidase inhibitors: Promising therapeutic agents for Alzheimer’s disease (Review)

Monoamine oxidase inhibitors: Promising therapeutic agents for Alzheimer’s disease (Review)

Astroglial Responses to Amyloid-Beta Progression in a Mouse Model of Alzheimer’s Disease

Evidence for Astrocytosis in Prodromal Alzheimer Disease Provided by 11C-Deuterium-L-Deprenyl: A Multitracer PET Paradigm Combining 11C-Pittsburgh Compound B and 18F-FDG

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Evidence for Astrocytosis in Prodromal Alzheimer Disease Provided by ¹¹C-Deuterium-L-Deprenyl: A Multitracer PET Paradigm Combining ¹¹C-Pittsburgh Compound B and ¹⁸F-FDG