18 results on '"Nan, Jie"'
Search Results
2. p85S6K sustains synaptic GluA1 to ameliorate cognitive deficits in Alzheimer’s disease
- Author
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Jia-Bing Li, Xiao-Yu Hu, Mu-Wen Chen, Cai-Hong Xiong, Na Zhao, Yan-Hui Ge, Hao Wang, Xiao-Ling Gao, Nan-Jie Xu, Lan-Xue Zhao, Zhi-Hua Yu, Hong-Zhuan Chen, and Yu Qiu
- Subjects
Alzheimer’s disease ,Cognition ,GluA1 subunit of AMPA receptors ,Ribosomal S6 protein kinase 1 ,85 kDa isoform ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Ribosomal protein S6 kinase 1 (S6K1) is a serine–threonine kinase that has two main isoforms: p70S6K (70-kDa isoform) and p85S6K (85-kDa isoform). p70S6K, with its upstream mammalian target of rapamycin (mTOR), has been shown to be involved in learning and memory and participate in the pathophysiology of Alzheimer’s disease (AD). However, the function of p85S6K has long been neglected due to its high similarity to p70S6k. The role of p85S6K in learning and memory is still largely unknown. Methods We fractionated the postsynaptic densities to illustrate the differential distribution of p85S6K and p70S6K. Coimmunoprecipitation was performed to unveil interactions between p85S6K and the GluA1 subunit of AMPA receptor. The roles of p85S6K in synaptic targeting of GluA1 and learning and memory were evaluated by specific knockdown or overexpression of p85S6K followed by a broad range of methodologies including immunofluorescence, Western blot, in situ proximity ligation assay, morphological staining and behavioral examination. Further, the expression level of p85S6K was measured in brains from AD patients and AD model mice. Results p85S6K, but not p70S6K, was enriched in the postsynaptic densities. Moreover, knockdown of p85S6K resulted in defective spatial and recognition memory. In addition, p85S6K could interact with the GluA1 subunit of AMPA receptor through synapse-associated protein 97 and A-kinase anchoring protein 79/150. Mechanistic studies demonstrated that p85S6K could directly phosphorylate GluA1 at Ser845 and increase the amount of GluA1 in synapses, thus sustaining synaptic function and spine densities. Moreover, p85S6K was found to be specifically decreased in the synaptosomal compartment in the brains of AD patients and AD mice. Overexpression of p85S6K ameliorated the synaptic deficits and cognitive impairment in transgenic AD model mice. Conclusions These results strongly imply a significant role for p85S6K in maintaining synaptic and cognitive function by interacting with GluA1. The findings provide an insight into the rational targeting of p85S6K as a therapeutic potential for AD.
- Published
- 2023
- Full Text
- View/download PDF
3. Amygdala neuronal dyshomeostasis via 5‐HT receptors mediates mood and cognitive defects in Alzheimer's disease.
- Author
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Wu, Xin‐Rong, Zhu, Xiao‐Na, Pan, Yuan‐Bo, Gu, Xue, Liu, Xian‐Dong, Chen, Si, Zhang, Yu, Xu, Tian‐Le, Xu, Nan‐Jie, and Sun, Suya
- Subjects
PYRAMIDAL neurons ,ALZHEIMER'S disease ,MEMORY disorders ,AFFECTIVE disorders ,COGNITION disorders ,INTERNEURONS ,SEROTONIN receptors - Abstract
Behavioral changes or neuropsychiatric symptoms (NPSs) are common features in dementia and are associated with accelerated cognitive impairment and earlier deaths. However, how NPSs are intertwined with cognitive decline remains elusive. In this study, we identify that the basolateral amygdala (BLA) is a key brain region that is associated with mood disorders and memory decline in the AD course. During the process from pre‐ to post‐onset in AD, the dysfunction of parvalbumin (PV) interneurons and pyramidal neurons in the amygdala leads to hyperactivity of pyramidal neurons in the basal state and insensitivity to external stimuli. We further demonstrate that serotonin (5‐HT) receptors in distinct neurons synergistically regulate the BLA microcircuit of AD rather than 5‐HT levels, in which both restrained inhibitory inputs by excessive 5‐HT1AR signaling in PV interneurons and depolarized pyramidal neurons via upregulated 5‐HT2AR contribute to aberrant neuronal hyperactivity. Downregulation of these two 5‐HT receptors simultaneously enables neurons to resist β‐amyloid peptides (Aβ) neurotoxicity and ameliorates the mood and cognitive defects. Therefore, our study reveals a crucial role of 5‐HT receptors for regulating neuronal homeostasis in AD pathogenesis, and this would provide early intervention and potential targets for AD cognitive decline. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
4. Differential microstructural and morphological abnormalities in mild cognitive impairment and Alzheimer's disease: Evidence from cortical and deep gray matter
- Author
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Gong, Nan‐Jie, Chan, Chun‐Chung, Leung, Lam‐Ming, Wong, Chun‐Sing, Dibb, Russell, and Liu, Chunlei
- Subjects
Biological Psychology ,Psychology ,Dementia ,Acquired Cognitive Impairment ,Aging ,Neurodegenerative ,Brain Disorders ,Neurosciences ,Alzheimer's Disease ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Biomedical Imaging ,2.1 Biological and endogenous factors ,Aetiology ,Neurological ,Aged ,Aged ,80 and over ,Alzheimer Disease ,Brain Mapping ,Cognitive Dysfunction ,Diffusion Magnetic Resonance Imaging ,Female ,Gray Matter ,Humans ,Image Processing ,Computer-Assisted ,Male ,Middle Aged ,Psychiatric Status Rating Scales ,Alzheimer's disease ,mild cognitive impairment ,diffusion kurtosis imaging ,diffusion tensor imaging ,gray matter ,volume ,cortical thickness ,microstructure ,Cognitive Sciences ,Experimental Psychology ,Biological psychology ,Cognitive and computational psychology - Abstract
One aim of this study is to use non-Gaussian diffusion kurtosis imaging (DKI) for capturing microstructural abnormalities in gray matter of Alzheimer's disease (AD). The other aim is to compare DKI metrics against thickness of cortical gray matter and volume of deep gray matter, respectively. A cohort of 18 patients with AD, 18 patients with amnestic mild cognitive impairment (MCI), and 18 normal controls underwent morphological and DKI MR imaging. Images were investigated using regions-of-interest-based analyses for deep gray matter and vertex-wise analyses for cortical gray matter. In deep gray matter, more regions showed DKI parametric abnormalities than atrophies at the early MCI stage. Mean kurtosis (MK) exhibited the largest number of significant abnormalities among all DKI metrics. At the later AD stage, diffusional abnormalities were observed in fewer regions than atrophies. In cortical gray matter, abnormalities in thickness were mainly in the medial and lateral temporal lobes, which fit the locations of known early pathological changes. Microstructural abnormalities were predominantly in the parietal and even frontal lobes, which fit the locations of known late pathological changes. In conclusion, MK can complement conventional diffusion metrics for detecting microstructural changes, especially in deep gray matter. This study also provides evidence supporting the notion that microstructural changes predate morphological changes. Hum Brain Mapp 38:2495-2508, 2017. © 2017 Wiley Periodicals, Inc.
- Published
- 2017
5. Targeting neuroplasticity in patients with neurodegenerative diseases using brain stimulation techniques
- Author
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Ti-Fei Yuan, Wei-Guang Li, Chencheng Zhang, Hongjiang Wei, Suya Sun, Nan-Jie Xu, Jun Liu, and Tian-Le Xu
- Subjects
Alzheimer’s disease ,Parkinson’s disease ,Synapse ,Neurotransmitter ,Synaptic plasticity ,Brain stimulation ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Deficits in synaptic transmission and plasticity are thought to contribute to the pathophysiology of Alzheimer’s disease (AD) and Parkinson’s disease (PD). Several brain stimulation techniques are currently available to assess or modulate human neuroplasticity, which could offer clinically useful interventions as well as quantitative diagnostic and prognostic biomarkers. In this review, we discuss several brain stimulation techniques, with a special emphasis on transcranial magnetic stimulation and deep brain stimulation (DBS), and review the results of clinical studies that applied these techniques to examine or modulate impaired neuroplasticity at the local and network levels in patients with AD or PD. The impaired neuroplasticity can be detected in patients at the earlier and later stages of both neurodegenerative diseases. However, current brain stimulation techniques, with a notable exception of DBS for PD treatment, cannot serve as adequate clinical tools to assist in the diagnosis, treatment, or prognosis of individual patients with AD or PD. Targeting the impaired neuroplasticity with improved brain stimulation techniques could offer a powerful novel approach for the treatment of AD and PD.
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- 2020
- Full Text
- View/download PDF
6. Paroxetine ameliorates prodromal emotional dysfunction and late-onset memory deficit in Alzheimer’s disease mice
- Author
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Peng-Hui Ai, Si Chen, Xian-Dong Liu, Xiao-Na Zhu, Yuan-Bo Pan, Dong-Fu Feng, Shengdi Chen, Nan-Jie Xu, and Suya Sun
- Subjects
Alzheimer’s disease ,Paroxetine treatment ,Glutamate receptor ,Memory deficit ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Neuropsychiatric symptoms (NPS) such as depression, anxiety, apathy, and irritability occur in prodromal phases of clinical Alzheimer’s disease (AD), which might be an increased risk for later developing AD. Here we treated young APP/PS1 AD model mice prophylactically with serotonin-selective re-uptake inhibitor (SSRI) paroxetine and investigated the protective role of anti-depressant agent in emotional abnormalities and cognitive defects during disease progress. Methods To investigate the protective role of paroxetine in emotional abnormalities and cognitive defects during disease progress, we performed emotional behaviors of 3 months old APP/PS1 mouse following oral administration of paroxetine prophylactically starting at 1 month of age. Next, we tested the cognitive, biochemical and pathological, effects of long term administration of paroxetine at 6 months old. Results Our results showed that AD mice displayed emotional dysfunction in the early stage. Prophylactic administration of paroxetine ameliorated the initial emotional abnormalities and preserved the eventual memory function in AD mice. Conclusion Our data indicate that prophylactic administration of paroxetine ameliorates the emotional dysfunction and memory deficit in AD mice. These neuroprotective effects are attributable to functional restoration of glutamate receptor (GluN2A) in AD mice.
- Published
- 2020
- Full Text
- View/download PDF
7. Quantitative Susceptibility Mapping: Contrast Mechanisms and Clinical Applications
- Author
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Liu, Chunlei, Wei, Hongjiang, Gong, Nan-Jie, Cronin, Matthew, Dibb, Russel, and Decker, Kyle
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Biomedical Imaging ,4.1 Discovery and preclinical testing of markers and technologies ,Detection ,screening and diagnosis ,Generic health relevance ,quantitative susceptibility mapping ,susceptibility tensor imaging ,brain ,iron ,myelin ,Parkinson disease ,multiple sclerosis ,Alzheimer disease ,Alzheimer's disease ,Parkinson's disease - Abstract
Quantitative susceptibility mapping (QSM) is a recently developed MRI technique for quantifying the spatial distribution of magnetic susceptibility within biological tissues. It first uses the frequency shift in the MRI signal to map the magnetic field profile within the tissue. The resulting field map is then used to determine the spatial distribution of the underlying magnetic susceptibility by solving an inverse problem. The solution is achieved by deconvolving the field map with a dipole field, under the assumption that the magnetic field is a result of the superposition of the dipole fields generated by all voxels and that each voxel has its unique magnetic susceptibility. QSM provides improved contrast to noise ratio for certain tissues and structures compared to its magnitude counterpart. More importantly, magnetic susceptibility is a direct reflection of the molecular composition and cellular architecture of the tissue. Consequently, by quantifying magnetic susceptibility, QSM is becoming a quantitative imaging approach for characterizing normal and pathological tissue properties. This article reviews the mechanism generating susceptibility contrast within tissues and some associated applications.
- Published
- 2015
8. Targeting neuroplasticity in patients with neurodegenerative diseases using brain stimulation techniques
- Author
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Yuan, Ti-Fei, Li, Wei-Guang, Zhang, Chencheng, Wei, Hongjiang, Sun, Suya, Xu, Nan-Jie, Liu, Jun, and Xu, Tian-Le
- Published
- 2020
- Full Text
- View/download PDF
9. Paroxetine ameliorates prodromal emotional dysfunction and late-onset memory deficit in Alzheimer’s disease mice
- Author
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Ai, Peng-Hui, Chen, Si, Liu, Xian-Dong, Zhu, Xiao-Na, Pan, Yuan-Bo, Feng, Dong-Fu, Chen, Shengdi, Xu, Nan-Jie, and Sun, Suya
- Published
- 2020
- Full Text
- View/download PDF
10. Targeting neuroplasticity in patients with neurodegenerative diseases using brain stimulation techniques
- Author
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Wei-Guang Li, Tian-Le Xu, Ti-Fei Yuan, Chencheng Zhang, Hongjiang Wei, Nan-Jie Xu, Jun Liu, and Suya Sun
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Deep brain stimulation ,Neurology ,Parkinson's disease ,Deep Brain Stimulation ,Cognitive Neuroscience ,medicine.medical_treatment ,Review ,Disease ,Synaptic plasticity ,lcsh:RC346-429 ,Stereotaxic Techniques ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Alzheimer Disease ,Neuroplasticity ,Animals ,Humans ,Medicine ,Neurotransmitter ,lcsh:Neurology. Diseases of the nervous system ,Neuronal Plasticity ,business.industry ,Brain ,Neurodegenerative Diseases ,Parkinson Disease ,medicine.disease ,Transcranial Magnetic Stimulation ,Synapse ,Transcranial magnetic stimulation ,030104 developmental biology ,Brain stimulation ,Parkinson’s disease ,Neurology (clinical) ,business ,Neuroscience ,Alzheimer’s disease ,030217 neurology & neurosurgery - Abstract
Deficits in synaptic transmission and plasticity are thought to contribute to the pathophysiology of Alzheimer’s disease (AD) and Parkinson’s disease (PD). Several brain stimulation techniques are currently available to assess or modulate human neuroplasticity, which could offer clinically useful interventions as well as quantitative diagnostic and prognostic biomarkers. In this review, we discuss several brain stimulation techniques, with a special emphasis on transcranial magnetic stimulation and deep brain stimulation (DBS), and review the results of clinical studies that applied these techniques to examine or modulate impaired neuroplasticity at the local and network levels in patients with AD or PD. The impaired neuroplasticity can be detected in patients at the earlier and later stages of both neurodegenerative diseases. However, current brain stimulation techniques, with a notable exception of DBS for PD treatment, cannot serve as adequate clinical tools to assist in the diagnosis, treatment, or prognosis of individual patients with AD or PD. Targeting the impaired neuroplasticity with improved brain stimulation techniques could offer a powerful novel approach for the treatment of AD and PD.
- Published
- 2020
11. Paroxetine ameliorates prodromal emotional dysfunction and late-onset memory deficit in Alzheimer’s disease mice
- Author
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Xian-Dong Liu, Xiao-Na Zhu, Sheng-Di Chen, Dong-Fu Feng, Nan-Jie Xu, Yuan-Bo Pan, Si Chen, Suya Sun, and Peng-Hui Ai
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Neurology ,Time Factors ,Cognitive Neuroscience ,Prodromal Symptoms ,Mice, Transgenic ,Paroxetine treatment ,Disease ,Irritability ,Neuroprotection ,Receptors, N-Methyl-D-Aspartate ,lcsh:RC346-429 ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Amyloid beta-Protein Precursor ,Mice ,0302 clinical medicine ,Alzheimer Disease ,Internal medicine ,Presenilin-1 ,Medicine ,Animals ,Apathy ,Affective Symptoms ,Memory deficit ,Depression (differential diagnoses) ,lcsh:Neurology. Diseases of the nervous system ,Memory Disorders ,business.industry ,Research ,Glutamate receptor ,Paroxetine ,030104 developmental biology ,Neuroprotective Agents ,Anxiety ,Neurology (clinical) ,medicine.symptom ,business ,Alzheimer’s disease ,030217 neurology & neurosurgery ,Selective Serotonin Reuptake Inhibitors ,medicine.drug - Abstract
Background Neuropsychiatric symptoms (NPS) such as depression, anxiety, apathy, and irritability occur in prodromal phases of clinical Alzheimer’s disease (AD), which might be an increased risk for later developing AD. Here we treated young APP/PS1 AD model mice prophylactically with serotonin-selective re-uptake inhibitor (SSRI) paroxetine and investigated the protective role of anti-depressant agent in emotional abnormalities and cognitive defects during disease progress. Methods To investigate the protective role of paroxetine in emotional abnormalities and cognitive defects during disease progress, we performed emotional behaviors of 3 months old APP/PS1 mouse following oral administration of paroxetine prophylactically starting at 1 month of age. Next, we tested the cognitive, biochemical and pathological, effects of long term administration of paroxetine at 6 months old. Results Our results showed that AD mice displayed emotional dysfunction in the early stage. Prophylactic administration of paroxetine ameliorated the initial emotional abnormalities and preserved the eventual memory function in AD mice. Conclusion Our data indicate that prophylactic administration of paroxetine ameliorates the emotional dysfunction and memory deficit in AD mice. These neuroprotective effects are attributable to functional restoration of glutamate receptor (GluN2A) in AD mice.
- Published
- 2020
12. The activated newborn neurons participate in enriched environment induced improvement of locomotor function in APP/PS1 mice
- Author
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Hui-Dong Tang, Nan-Jie Xu, Qiongqiong Li, Hualong Wang, Jianqing Ding, Sheng-Di Chen, and Suya Sun
- Subjects
Male ,medicine.medical_specialty ,Elevated plus maze ,Neurogenesis ,Hippocampus ,Mice, Transgenic ,Motor Activity ,050105 experimental psychology ,lcsh:RC321-571 ,03 medical and health sciences ,Behavioral Neuroscience ,Mice ,0302 clinical medicine ,Cognition ,Internal medicine ,Physical Stimulation ,Neuroplasticity ,mental disorders ,Medicine ,elevated plus maze ,Animals ,0501 psychology and cognitive sciences ,Maze Learning ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Original Research ,Neurons ,Environmental enrichment ,Behavior, Animal ,business.industry ,Dentate gyrus ,05 social sciences ,locomotor function ,Fear ,Alzheimer's disease ,Endocrinology ,nervous system ,Animals, Newborn ,Dentate Gyrus ,Models, Animal ,Conditioning ,business ,030217 neurology & neurosurgery ,enriched environment - Abstract
Introduction Alzheimer's disease (AD) is an age‐related neurodegenerative disorder. One of the pathological features of AD is neuronal loss in brain regions associated with cognition, particularly the hippocampus. An enriched environment (EE) can facilitate neuronal plasticity and improve behaviors such as emotion, motor function, and cognition in AD. Methods After APP/PS1 mice were exposed to EE at an early stage (2 months of age), elevated plus maze performance and contextual fear conditioning were tested, and neurogenesis and the extent of activation in the hippocampus were observed. Results The results showed that, compared with that in the mice that experienced a standard environment, the cognition of the mice exposed to EE, as measured by contextual fear conditioning, was not statistically significant. However, based on their performance in the elevated plus maze, the index was increased in the mice, especially the APP/PS1 mice, exposed to EE. Consistent with the behavioral changes, the APP/PS1 mice exposed to EE showed an increased number of c‐Fos‐positive neurons and elevated neurogenesis in the dentate gyrus (DG) area. In addition, the activation of newborn neurons did not occur in the other three groups. Conclusions These results indicate that the activation of newborn neurons may participate in the improvement of behavioral performance in APP/PS1 mice after EE.
- Published
- 2019
13. Differential microstructural and morphological abnormalities in mild cognitive impairment and Alzheimer's disease: Evidence from cortical and deep gray matter
- Author
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Gong, Nan-Jie, Chan, Chun-Chung, Leung, Lam-Ming, Wong, Chun-Sing, Dibb, Russell, and Liu, Chunlei
- Subjects
Male ,diffusion kurtosis imaging ,Aging ,Image Processing ,microstructure ,Neurodegenerative ,Alzheimer's Disease ,Computer-Assisted ,mild cognitive impairment ,Alzheimer Disease ,80 and over ,Acquired Cognitive Impairment ,Humans ,2.1 Biological and endogenous factors ,Cognitive Dysfunction ,Gray Matter ,Aetiology ,Aged ,Psychiatric Status Rating Scales ,Brain Mapping ,volume ,Neurosciences ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Experimental Psychology ,Middle Aged ,cortical thickness ,diffusion tensor imaging ,Brain Disorders ,Diffusion Magnetic Resonance Imaging ,Neurological ,Biomedical Imaging ,Female ,Dementia ,Cognitive Sciences - Abstract
One aim of this study is to use non-Gaussian diffusion kurtosis imaging (DKI) for capturing microstructural abnormalities in gray matter of Alzheimer's disease (AD). The other aim is to compare DKI metrics against thickness of cortical gray matter and volume of deep gray matter, respectively. A cohort of 18 patients with AD, 18 patients with amnestic mild cognitive impairment (MCI), and 18 normal controls underwent morphological and DKI MR imaging. Images were investigated using regions-of-interest-based analyses for deep gray matter and vertex-wise analyses for cortical gray matter. In deep gray matter, more regions showed DKI parametric abnormalities than atrophies at the early MCI stage. Mean kurtosis (MK) exhibited the largest number of significant abnormalities among all DKI metrics. At the later AD stage, diffusional abnormalities were observed in fewer regions than atrophies. In cortical gray matter, abnormalities in thickness were mainly in the medial and lateral temporal lobes, which fit the locations of known early pathological changes. Microstructural abnormalities were predominantly in the parietal and even frontal lobes, which fit the locations of known late pathological changes. In conclusion, MK can complement conventional diffusion metrics for detecting microstructural changes, especially in deep gray matter. This study also provides evidence supporting the notion that microstructural changes predate morphological changes. Hum Brain Mapp 38:2495-2508, 2017. © 2017 Wiley Periodicals, Inc.
- Published
- 2017
14. Quantitative Susceptibility Mapping: Contrast Mechanisms and Clinical Applications
- Author
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Hongjiang Wei, Matthew J. Cronin, Kyle Decker, Russel Dibb, Chunlei Liu, and Nan-Jie Gong
- Subjects
Materials science ,Field (physics) ,Parkinson's disease ,brain ,Physics::Medical Physics ,computer.software_genre ,multiple sclerosis ,Article ,030218 nuclear medicine & medical imaging ,susceptibility tensor imaging ,03 medical and health sciences ,0302 clinical medicine ,Nuclear magnetic resonance ,iron ,Contrast-to-noise ratio ,Voxel ,Radiology, Nuclear Medicine and imaging ,quantitative susceptibility mapping ,Quantitative susceptibility mapping ,Alzheimer's disease ,equipment and supplies ,Magnetic susceptibility ,Magnetic field ,Dipole ,myelin ,computer ,Magnetic dipole ,human activities ,030217 neurology & neurosurgery - Abstract
Quantitative susceptibility mapping (QSM) is a recently developed magnetic resonance imaging (MRI) technique for quantifying the spatial distribution of magnetic susceptibility within biological tissues. It first uses the frequency shift in the MRI signal to map the magnetic field profile within the tissue. The resulting field map is then used to determine the spatial distribution of the underlying magnetic susceptibility by solving an inverse problem. The solution is achieved by deconvolving the field map with a dipole field, under the assumption that the magnetic field results from a superposition of the dipole fields generated by all voxels and that each voxel has its own unique magnetic susceptibility. QSM provides an improved contrast-to-noise ratio for certain tissues and structures compared with its magnitude counterpart. More importantly, magnetic susceptibility directly reflects the molecular composition and cellular architecture of the tissue. Consequently, by quantifying magnetic susceptibility, QSM is becoming a quantitative imaging approach for characterizing normal and pathological tissue properties. This article reviews the mechanism that generates susceptibility contrast within tissues and some associated applications.
- Published
- 2016
15. Imaging beta amyloid aggregation and iron accumulation in Alzheimer's disease using quantitative susceptibility mapping MRI.
- Author
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Gong, Nan-Jie, Dibb, Russell, Bulk, Marjolein, van der Weerd, Louise, and Liu, Chunlei
- Subjects
- *
ALZHEIMER'S disease , *AMYLOID beta-protein precursor , *ALZHEIMER'S disease diagnosis , *AMYLOID plaque , *NEUROFIBRILLARY tangles - Abstract
Abstract Beta amyloid is a protein fragment snipped from the amyloid precursor protein (APP). Aggregation of these peptides into amyloid plaques is one of the hallmarks of Alzheimer's disease. MR imaging of beta amyloid plaques has been attempted using various techniques, notably with T2* contrast. The non-invasive detectability of beta amyloid plaques in MR images has so far been largely attributed to focal iron deposition accompanying the plaques. It is believed that the T2* shortening effects of paramagnetic iron are the primary source of contrast between plaques and surrounding tissue. Amyloid plaque itself has been reported to induce no magnetic susceptibility effect. We hypothesized that aggregations of beta amyloid would increase electron density and induce notable changes in local susceptibility value, large enough to generate contrast relative to surrounding normal tissues that can be visualized by quantitative susceptibility mapping (QSM) MR imaging. To test this hypothesis, we first demonstrated in a phantom that beta amyloid is diamagnetic and can generate strong contrast on susceptibility maps. We then conducted experiments on a transgenic mouse model of Alzheimer's disease that is known to mimic the formation of human beta amyloid but without neurofibrillary tangles or neuronal death. Over a period of 18 months, we showed that QSM can be used to longitudinally monitor beta amyloid accumulation and accompanied iron deposition in vivo. Individual beta amyloid plaque can also be visualized ex vivo in high resolution susceptibility maps. Moreover, the measured negative susceptibility map and positive susceptibility map could provide histology-like image contrast for identifying deposition of beta amyloid plaques and iron. Finally, we demonstrated that the diamagnetic susceptibility of beta amyloid can also be observed in brain specimens of AD patients. The ability to assess beta amyloid aggregation non-invasively with QSM MR imaging may aid the diagnosis of Alzheimer's disease. Highlights • We demonstrated in a phantom experiment that beta amyloid has diamagnetic susceptibility contrary to previous hypothesis. • This diamagnetic susceptibility can be measured and used to monitor longitudinal accumulation of beta amyloid in a mouse model and even visualize individual plaques. • The diamagnetic susceptibility map provided image contrast for identifying dominating magnetic sources of beta amyloid plaques, which were validated by histology. • The ability to image and quantify beta amyloid aggregation non-invasively with MRI may aid the diagnosis of Alzheimer's disease. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
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16. Aging in deep gray matter and white matter revealed by diffusional kurtosis imaging.
- Author
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Nan-Jie Gong, Chun-Sing Wong, Chun-Chung Chan, Lam-Ming Leung, and Yiu-Ching Chu
- Subjects
- *
AGING , *PERIAQUEDUCTAL gray matter , *WHITE matter (Nerve tissue) , *DIFFUSION tensor imaging , *MICROSTRUCTURE , *ISOTROPIC properties , *NEUROBIOLOGY - Abstract
Diffusion tensor imaging has already been extensively used to probe microstructural alterations in white matter tracts, and scarcely, in deep gray matter. However, results in literature regarding age-related degenerative mechanisms in white matter tracts and parametric changes in the putamen are inconsistent. Diffusional kurtosis imaging is a mathematical extension of diffusion tensor imaging, which could more comprehensively mirror microstructure, particularly in isotropic tissues such as gray matter. In this study, we used the diffusional kurtosis imaging method and a white-matter model that provided metrics of explicit neurobiological interpretations in healthy participants (58 in total, aged from 25 to 84 years). Tract-based whole-brain analyses and regions-of-interest (anterior and posterior limbs of the internal capsule, cerebral peduncle, fornix, genu and splenium of corpus callosum, globus pallidus, substantia nigra, red nucleus, putamen, caudate nucleus, and thalamus) analyses were performed to examine parametric differences across regions and correlations with age. In white matter tracts, evidence was found supportive for anterior-posterior gradient and not completely supportive for retrogenesis theory. Age-related degenerations appeared to be broadly driven by axonal loss. Demyelination may also be a major driving mechanism, although confined to the anterior brain. In terms of deep gray matter, higher mean kurtosis and fractional anisotropy in the globus pallidus, substantia nigra, and red nucleus reflected higher microstructural complexity and directionality compared with the putamen, caudate nucleus, and thalamus. In particular, the unique age-related positive correlations for fractional anisotropy, mean kurtosis, and radial kurtosis in the putamen opposite to those in other regions call for further investigation of exact underlying mechanisms. In summary, the results suggested that diffusional kurtosis can provide measurements in a new dimension that were complementary to diffusivity metrics. Kurtosis together with diffusivity can more comprehensively characterize microstructural compositions and age-related changes than diffusivity alone. Combined with proper model, it may also assist in providing neurobiological interpretations of the identified alterations. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
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17. Correlations between microstructural alterations and severity of cognitive deficiency in Alzheimer's disease and mild cognitive impairment: a diffusional kurtosis imaging study
- Author
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Gong, Nan-Jie, Wong, Chun-Sing, Chan, Chun-Chung, Leung, Lam-Ming, and Chu, Yiu-Ching
- Subjects
- *
ALZHEIMER'S disease , *MICROSTRUCTURE , *COGNITIVE ability , *MILD cognitive impairment , *DIAGNOSTIC imaging , *ALZHEIMER'S disease diagnosis , *ANISOTROPY - Abstract
Abstract: Object: Diffusional kurtosis imaging (DKI), a natural extension of diffusion tensor imaging (DTI), can characterize non-Gaussian diffusion in the brain. We investigated the capability of DKI parameters for detecting microstructural changes in both gray matter (GM) and white matter (WM) in patients with mild cognitive impairment (MCI) and Alzheimer''s disease (AD) and sought to determine whether these DKI parameters could serve as imaging biomarkers to indicate the severity of cognitive deficiency. Materials and Methods: DKI was performed on 18AD patients and 12 MCI patients. Fractional anisotropy, kurtosis and diffusivity parameters in the temporal, parietal, frontal and occipital lobes were compared between the two groups using Mann–Whitney U test. The correlations between regional DKI parameters and mini-mental state examination (MMSE) score were tested using Pearson''s correlation. Results: In ADs, significantly increased diffusivity and decreased kurtosis parameters were observed in both the GM and WM of the parietal and occipital lobes as compared to MCIs. Significantly decreased fractional anisotropy was also observed in the WM of these lobes in ADs. With the exception of fractional anisotropy and radial kurtosis, all the five other DKI parameters exhibited significant correlations with MMSE score in both GM and WM. Conclusion: Bearing additional information, the DKI model can provide sensitive imaging biomarkers for assessing the severity of cognitive deficiency in reference to MMSE score and potentially improve early detection and progression monitoring of AD based on characterizing microstructures in both the WM and especially the GM. [Copyright &y& Elsevier]
- Published
- 2013
- Full Text
- View/download PDF
18. Reduced Synaptic STIM2 Expression and Impaired Store-Operated Calcium Entry Cause Destabilization of Mature Spines in Mutant Presenilin Mice.
- Author
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Sun, Suya, Zhang, Hua, Liu, Jie, Popugaeva, Elena, Xu, Nan-Jie, Feske, Stefan, White, Charles?L., and Bezprozvanny, Ilya
- Subjects
- *
DENDRITES , *ALZHEIMER'S disease , *CALMODULIN , *GENETIC mutation , *NEURAL physiology , *PRESENILINS , *PHYSIOLOGICAL effects of calcium , *GENE expression , *CELLULAR aging , *LABORATORY mice - Abstract
Summary: Mushroom dendritic spine structures are essential for memory storage, and the loss of mushroom spines may explain memory defects in Alzheimer’s disease (AD). Here we show a significant reduction in the fraction of mushroom spines in hippocampal neurons from the presenilin-1 M146V knockin (KI) mouse model of familial AD (FAD). The stabilization of mushroom spines depends on STIM2-mediated neuronal store-operated calcium influx (nSOC) and continuous activity of Ca2+/calmodulin-dependent protein kinase II (CaMKII). We demonstrate that STIM2-nSOC-CaMKII pathway is compromised in KI neurons, in aging neurons, and in sporadic AD brains due to downregulation of STIM2 protein. We further establish that overexpression of STIM2 rescues synaptic nSOC, CaMKII activity, and mushroom spine loss in KI neurons. Our results identify STIM2-nSOC-CaMKII synaptic maintenance pathway as a novel potential therapeutic target for treatment of AD and age-related memory decline. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
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