Evaluation of Monoamine Oxidase-A as a New Biomarker for Alzheimer's Disease
单胺氧化酶 A 作为阿尔茨海默病新生物标志物的评价
基本信息
- 批准号:10525579
- 负责人:
- 金额:$ 43.18万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-01 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AldehydesAlzheimer&aposs DiseaseAlzheimer&aposs disease brainAlzheimer&aposs disease patientAlzheimer’s disease biomarkerAmmoniaAmyloid beta-ProteinAnimalsAnteriorAntidepressive AgentsApplications GrantsArizonaAttentionAutopsyAutoradiographyBindingBiogenic AminesBiological MarkersBrainBrain imagingBrain regionChemicalsChronicClorgylineCognitiveCytosolDementiaDiagnosisDioxygenDiseaseDopamineDrug EvaluationEnzymesEtiologyEvaluationExhibitsFeasibility StudiesFlavoproteinsFluorineFluoxetineGoalsGrantHarmineHealthHippocampus (Brain)HumanHydrogen PeroxideHyperactivityHypoxiaImageIn VitroInflammationInflammation MediatorsInflammatory ResponseInterleukin-13Interleukin-4LabelMajor Depressive DisorderMeasuresMental DepressionMicrogliaMitochondriaMolecularMonoamine Oxidase ANeocortexNerve DegenerationNeurodegenerative DisordersNeurofibrillary TanglesNeuronsNeurotransmittersNorepinephrineOuter Mitochondrial MembraneOxidative StressPatientsPeripheralPlayPositron-Emission TomographyProductionProtein IsoformsProteinsRadioisotopesReactionReactive Oxygen SpeciesReportingResearchResearch InstituteRodentRoleSamplingSenile PlaquesSerotoninSliceStainsTemporal LobeTranslationsUp-RegulationX ChromosomeYanganalogbasebrain tissueclinical anxietydisorder controldrug developmententorhinal cortexgenetic signaturehuman tissueimaging agentimaging approachimaging biomarkerimaging modalityimaging studyinflammatory markerinhibitorinhibitor therapymacrophagemonoaminemonocytepaired helical filamentpotential biomarkerprotein degradationradiotracerresponsetau Proteinstau-1therapeutic developmenttherapeutically effectivetreatment planning
项目摘要
Evaluation of Monoamine Oxidase-A as a New Biomarker for Alzheimer's Disease
Project Summary
This application is in response to PAR-19-071, “Research on current topics in Alzheimer's disease and its
related dementias (ADRD)”. Alzheimer's disease (AD) is a neurodegenerative disease characterized by Aβ
plaque aggregation and Tau protein paired helical filaments causing neurofibrillary tangles (NFT) in the brain.
Noninvasive brain imaging methods and peripheral measures of phosphorylated Tau isoforms (pTau181 and
pTau217) are becoming reliable markers for AD. In addition to these biomarkers, translocator protein (TSPO)
as a marker for inflammation is also being pursued in efforts to gain a comprehensive understanding of
disease etiology. Imaging methods play a key role in understanding NFT accumulation in AD beginning in the
entorhinal cortex and hippocampus, spreading to the temporal cortex and subsequently to the neocortex.
Monoamine oxidase A (MAO-A), a mitochondrial enzyme found in neurons, deaminates monoamine
neurotransmitters. Upregulation of MAO-A can cause oxidative stress leading to neurodegeneration. Currently,
no PET imaging studies have been reported on MAO-A in AD patients. [11C]Harmine, a MAO-A PET
radiotracer has been used in human studies of depression, but no reports exist in AD. In autoradiographic
studies using [18F]FEH (an analog of harmine for MAO-A) and [18F]FAZIN3 (binds to MAO-A), we have
compared MAO-A in anterior cingulate in AD and control (CN) subjects. Our preliminary findings show >100%
increase of MAO-A in anterior cingulate in postmortem AD brain subjects, and this increase in MAO-A
positively correlated with increases in Tau, Aβ and TSPO. This may suggest greater neurotransmitter
breakdown, increased production of reactive oxygen species, potentially causing protein degradation,
aggregation and inflammation in AD. In order to ascertain a role of MAO-A in AD and compliment current
imaging approaches in understanding Aβ and NFT accumulation in AD, we propose to carry out a detailed
postmortem study in AD subjects to confirm MAO-A upregulation. Our goal is to examine anterior cingulate and
hippocampus in AD and CN subjects, two brain regions where MAO-A has been studied with [11C]Harmine. In
addition to [18F]FAZIN3 and [18F]FEH, we will also use [3H]Harmine (chemically identical to [11C]Harmine,
except for the radioisotope). Positive findings with [3H]Harmine will support and provide impetus for PET
studies in AD using [11C]Harmine, without much delay, since it is already approved for human use. For the two
brain regions, comparisons between the biomarkers will be carried out to support the hypothesis that MAO-A is
upregulated in AD and positively correlated with Tau, Aβ and TSPO measures of the same subjects. Impact of
our findings will support PET imaging studies of MAO-A in AD subjects and may have the potential for AD drug
development of MAO-A inhibitors for therapeutic purposes.
单胺氧化酶- a作为阿尔茨海默病新生物标志物的评价
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Jogeshwar Mukherjee其他文献
Jogeshwar Mukherjee的其他文献
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{{ truncateString('Jogeshwar Mukherjee', 18)}}的其他基金
Fluorine-18 Labeled Functional Dopamine Receptor Imaging Agents
氟 18 标记的功能性多巴胺受体显像剂
- 批准号:
8974173 - 财政年份:2015
- 资助金额:
$ 43.18万 - 项目类别:
Fluorine-18 Labeled Functional Dopamine Receptor Imaging Agents
氟 18 标记的功能性多巴胺受体显像剂
- 批准号:
9066618 - 财政年份:2015
- 资助金额:
$ 43.18万 - 项目类别:
Imaging Adrenergic Stimulation of Brown Adipose Tissue
棕色脂肪组织的肾上腺素刺激成像
- 批准号:
8324521 - 财政年份:2011
- 资助金额:
$ 43.18万 - 项目类别:
18F-Mefway for Imaging Mood Disorders and Alzheimer's Disease
18F-Mefway 用于情绪障碍和阿尔茨海默病的成像
- 批准号:
7434384 - 财政年份:2007
- 资助金额:
$ 43.18万 - 项目类别:
PET Imaging Agents for a4b2 Nicotinic Receptors
a4b2 烟碱受体 PET 显像剂
- 批准号:
9264445 - 财政年份:2007
- 资助金额:
$ 43.18万 - 项目类别:














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