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1. 发明申请

US20140038186A1 ALZHEIMER'S DISEASE-SPECIFIC ALTERATIONS OF PROTEIN KINASE C EPSILON (PKC-EPSILON) PROTEIN LEVELS 审中-公开
标题翻译：蛋白激酶C蛋白激酶（PKC-EPSILON）蛋白水平的ALZHEIMER疾病特异性改变
公开(公告)号：US20140038186A1
公开(公告)日：2014-02-06
申请号：US13580431
申请日：2011-02-22
申请人： Tapan Kumar Khan , Daniel L. Alkon
发明人： Tapan Kumar Khan , Daniel L. Alkon
IPC分类号： C12Q1/48 , G01N33/573 , C12Q1/68
CPC分类号： C12Q1/485 , C12Q1/68 , C12Q1/6883 , G01N33/573 , G01N33/6896 , G01N2333/912 , G01N2800/2821
摘要： The present invention relates to methods of diagnosing Alzheimer's Disease in a human patient by detecting alterations in the ratio of PKC epsilon protein levels in a human patient compared with PKC epsilon levels in a control subject. The Alzheimer's disease-specific molecular biomarkers disclosed herein are useful for the diagnosis of Alzheimer's disease and for screening methods for the identification of compounds for treating or preventing Alzheimer's disease. The present invention also provides methods for elevating PKC epsilon protein levels comprising the steps of contacting one or more human cells with an amount of a PKC activator effective to elevate PKC epsilon levels compared to an uncontacted human cell.
摘要翻译：本发明涉及通过检测人类患者中PKCε蛋白水平与对照受试者中的PKCε水平相比的变化来诊断人类患者中的阿尔茨海默病的方法。本文公开的阿尔茨海默病特异性分子生物标志物可用于诊断阿尔茨海默病和用于鉴定用于治疗或预防阿尔茨海默氏病的化合物的筛选方法。本发明还提供了用于升高PKCε蛋白水平的方法，其包括以下步骤：使一个或多个人细胞与一定量的PKC激活剂相接触，以有效提高PKCε水平与未接触的人细胞相比。

2. 发明申请

US20110136144A1 FIBROBLAST GROWTH PATTERNS FOR DIAGNOSIS OF ALZHEIMER'S DISEASE 有权
标题翻译：用于诊断阿尔茨海默病的纤维细胞生长模式
公开(公告)号：US20110136144A1
公开(公告)日：2011-06-09
申请号：US12896862
申请日：2010-10-02
申请人： Florin Valentin Chirila , Tapan Kumar Khan , Daniel L. Alkon
发明人： Florin Valentin Chirila , Tapan Kumar Khan , Daniel L. Alkon
IPC分类号： G01N33/567 , C12Q1/02 , C40B40/02
CPC分类号： G01N33/5091 , G01N33/6896 , G01N2800/2821
摘要： Methods of diagnosing Alzheimer's disease are provided. At least five methods of diagnostic measurements are presented: Method 1: Integrated score; Method 2: Average aggregate area per number of aggregates; Method 3: Cell migration analysis; Method 4; Fractal analysis; Method 5: Lacunarity Analysis. In certain embodiments, a sample of a subject's skin provides a network of fibroblasts that is imaged and a fractal dimension of the image is calculated. The fractal dimension can be compared to an aged-matched control (non-Alzheimer's) database to determine if the subject has Alzheimer's disease. The network of fibroblasts may be cultured in a matrix, for example in a protein mixture.
摘要翻译：提供了诊断阿尔茨海默病的方法。提出了至少五种诊断测量方法：方法1：综合评分; 方法2：每个聚集体的平均聚集面积; 方法3：细胞迁移分析; 方法4; 分形分析; 方法5：Lacunarity分析。在某些实施方案中，受试者皮肤的样品提供成像的成纤维细胞的网络，并且计算图像的分形维数。可以将分形维数与老年匹配对照（非阿尔茨海默病）数据库进行比较，以确定受试者是否患有阿尔茨海默氏病。成纤维细胞的网络可以在基质中培养，例如在蛋白质混合物中。

3. 发明申请

US20080221042A1 Alzheimer's disease-specific alterations of the ERK1/ERK2 Phosphorylation ratio-Alzheimer's disease-specific molecular biomarkers (ADSMB) 审中-公开
标题翻译： ERK1 / ERK2磷酸化比例的阿尔茨海默病特异性改变 - 阿尔茨海默病特异性分子生物标志物（ADSMB）
公开(公告)号：US20080221042A1
公开(公告)日：2008-09-11
申请号：US12078857
申请日：2008-04-07
申请人： Tapan Kumar Khan , Daniel L. Alkon
发明人： Tapan Kumar Khan , Daniel L. Alkon
IPC分类号： A61K38/08 , C12Q1/02 , A61P25/28
CPC分类号： G01N33/6896 , A61K38/043 , A61K38/095 , A61K38/105 , A61K38/2207 , A61K38/4833 , G01N2800/2821 , G01N2800/52
摘要： The present invention relates to methods of diagnosing Alzheimer's Disease as well as to methods of confirming the presence or absence of Alzheimer's Disease in a subject. The present invention is also directed to methods of identifying a lead compound useful for the treatment of Alzheimer's Disease by contacting non-Alzheimer's cells with an amyloid beta peptide, stimulating the cells with a protein kinase C activator, contacting the cells with a test compound, and determining the value of an Alzheimer's Disease-specific molecular biomarker. The present invention is also directed to methods of diagnosing Alzheimer's Disease in a subject by detecting alterations in the ratio of specific phosphorylated MAP kinase proteins in cells after stimulation with a protein kinase C activator. The Alzheimer's Disease-specific molecular biomarkers disclosed herein are useful for the diagnosis of Alzheimer's Disease, monitoring the progression of Alzheimer's Disease in a subject and in screening methods for the identification of compounds for treating or preventing Alzheimer's Disease. The invention is also directed to kits containing reagents for the detection and diagnosis of the presence or absence of Alzheimer's Disease using the Alzheimer's Disease-specific molecular biomarkers disclosed herein.
摘要翻译：本发明涉及诊断阿尔茨海默病的方法以及确认受试者中是否存在阿尔茨海默氏病的方法。本发明还涉及通过使非阿尔茨海默病细胞与淀粉状蛋白β肽接触，用蛋白激酶C激活剂刺激细胞，使细胞与测试化合物接触来鉴定用于治疗阿尔茨海默病的铅化合物的方法，并确定阿尔茨海默氏病特异性分子生物标志物的价值。本发明还涉及通过检测用蛋白激酶C激活剂刺激后细胞中特异性磷酸化MAP激酶蛋白的比例变化来诊断受试者中的阿尔茨海默氏病的方法。本文公开的阿尔茨海默病特异性分子生物标志物可用于诊断阿尔茨海默氏病，监测受试者中阿尔茨海默氏病的进展和用于鉴定用于治疗或预防阿尔茨海默氏病的化合物的筛选方法。本发明还涉及包含用于使用本文公开的阿尔茨海默病特异性分子生物标志物来检测和诊断阿尔茨海默氏病或不存在的试剂的试剂盒。

4. 发明授权

US10317396B2 Peripheral diagnostic methods for screening Alzheimer's disease using beta amyloid and intercellular communication 有权
公开(公告)号：US10317396B2
公开(公告)日：2019-06-11
申请号：US14116138
申请日：2012-05-11
申请人： Florin V. Chirila , Tapan Kumar Khan , Daniel L. Alkon
发明人： Florin V. Chirila , Tapan Kumar Khan , Daniel L. Alkon
IPC分类号： G01N33/50
摘要： The present disclosure relates to a peripheral diagnostic method for screening Alzheimer's disease in patients based on quantitatively measured complexity of skin-sampled fibroblast networks.

5. 发明申请

US20110212474A1 ABNORMAL ALTERATIONS OF PKC ISOZYMES PROCESSING IN ALZHEIMER'S DISEASE PERIPHERAL CELLS 审中-公开
标题翻译：阿尔茨海默病外周血细胞中PKC异构体加工异常改变
公开(公告)号：US20110212474A1
公开(公告)日：2011-09-01
申请号：US12895957
申请日：2010-10-01
申请人： Tapan Kumar Khan , Daniel L. Alkon
发明人： Tapan Kumar Khan , Daniel L. Alkon
IPC分类号： C12Q1/48
CPC分类号： G01N33/6896 , G01N2333/9121 , G01N2800/2821
摘要： The present invention provides a method for the diagnosis of AD from non-AD conditions by using a PKC Isozyme Index obtained by determining ratios of ratios of different PKC Isozymes in peripheral cells of a test subject in the absence and presence of a beta-amyloid peptide, and optionally, in the presence of a PKC activator.
摘要翻译：本发明提供了一种通过使用通过确定在不存在和存在β-淀粉状蛋白肽的情况下测试受试者的外周细胞中不同PKC同功酶的比例的比例而获得的PKC同工酶指数来从非AD病症诊断AD的方法，并且任选地，在PKC激活剂的存在下。

6. 发明授权

US08658134B2 Fibroblast growth patterns for diagnosis of Alzheimer's disease 有权
标题翻译：成纤维细胞生长模式用于诊断阿尔茨海默病
公开(公告)号：US08658134B2
公开(公告)日：2014-02-25
申请号：US12896862
申请日：2010-10-02
申请人： Florin Valentin Chirila , Tapan Kumar Khan , Daniel L. Alkon
发明人： Florin Valentin Chirila , Tapan Kumar Khan , Daniel L. Alkon
IPC分类号： G01N33/483 , C12N5/07
CPC分类号： G01N33/5091 , G01N33/6896 , G01N2800/2821
摘要： Methods of diagnosing Alzheimer's disease are provided. At least five methods of diagnostic measurements are presented: Method 1: Integrated score; Method 2: Average aggregate area per number of aggregates; Method 3: Cell migration analysis; Method 4; Fractal analysis; Method 5: Lacunarity Analysis. In certain embodiments, a sample of a subject's skin provides a network of fibroblasts that is imaged and a fractal dimension of the image is calculated. The fractal dimension can be compared to an aged-matched control (non-Alzheimer's) database to determine if the subject has Alzheimer's disease. The network of fibroblasts may be cultured in a matrix, for example in a protein mixture.
摘要翻译：提供了诊断阿尔茨海默病的方法。提出了至少五种诊断测量方法：方法1：综合评分; 方法2：每个聚集体的平均聚集面积; 方法3：细胞迁移分析; 方法4; 分形分析; 方法5：Lacunarity分析。在某些实施方案中，受试者皮肤的样品提供成像的成纤维细胞的网络，并且计算图像的分形维数。可以将分形维数与老年匹配对照（非阿尔茨海默病）数据库进行比较，以确定受试者是否患有阿尔茨海默氏病。成纤维细胞的网络可以在基质中培养，例如在蛋白质混合物中。

7. 发明授权

US08822166B2 Stimulus-elicited genomic profile markers of alzheimer's disease 有权
标题翻译：刺激引起的阿尔茨海默病的基因组谱图标记
公开(公告)号：US08822166B2
公开(公告)日：2014-09-02
申请号：US12510707
申请日：2009-07-28
申请人： Daniel L. Alkon , Tapan Kumar Khan
发明人： Daniel L. Alkon , Tapan Kumar Khan
IPC分类号： G01N33/567 , G01N33/561
CPC分类号： C12Q1/6883 , C12Q2600/136 , C12Q2600/158 , G01N2800/2821
摘要： The present invention relates to a method for diagnosing Alzheimer's Disease (AD) using PKC-elicited gene expression profiles. PKC-activation elicits different genomic profiles in AD cells, as compared with control cells, which can be used to diagnose AD and individuals at risk for developing AD.
摘要翻译：本发明涉及使用PKC诱导的基因表达谱来诊断阿尔茨海默病（AD）的方法。与对照细胞相比，PKC激活引起AD细胞中的不同基因组谱，其可用于诊断AD和处于发展AD的风险的个体。

8. 发明申请

US20100021913A1 Stimulus-Elicited Genomic Profile Markers of Alzheimer's Disease 有权
标题翻译：激素诱发的阿尔茨海默病基因组分布标记
公开(公告)号：US20100021913A1
公开(公告)日：2010-01-28
申请号：US12510707
申请日：2009-07-28
申请人： Daniel L. Alkon , Tapan Kumar Khan
发明人： Daniel L. Alkon , Tapan Kumar Khan
IPC分类号： C12Q1/68 , C40B30/00 , C40B30/06
CPC分类号： C12Q1/6883 , C12Q2600/136 , C12Q2600/158 , G01N2800/2821
摘要： The present invention relates to a method for diagnosing Alzheimer's Disease (AD) using PKC-elicited gene expression profiles PKC-activation elicits different genomic profiles in AD cells, as compared with control cells, which can he used to diagnose AD and individuals at risk for developing AD.
摘要翻译：本发明涉及使用PKC诱导的基因表达谱来诊断阿尔茨海默病（AD）的方法PKC-活化引起AD细胞中不同的基因组谱，与对照细胞相比，其可以用于诊断AD和患有风险的个体开发AD。

9. 发明授权

US07595167B2 Alzheimer's disease-specific alterations of the Erk1/Erk2 phosphorylation ratio 有权
标题翻译： Erk1 / Erk2磷酸化比例的阿尔茨海默病特异性改变
公开(公告)号：US07595167B2
公开(公告)日：2009-09-29
申请号：US11246524
申请日：2005-10-11
申请人： Tapan Kumar Khan , Daniel L. Alkon
发明人： Tapan Kumar Khan , Daniel L. Alkon
IPC分类号： G01N33/567 , G01N33/561
CPC分类号： G01N33/6896 , G01N2800/2821
摘要： The present invention is directed to a method of diagnosing Alzheimer's disease in a subject by detecting alterations in the ratio of specific phosphorylated MAP kinase proteins in cells after stimulation with a protein kinase C activator. The Alzheimer's disease-specific molecular biomarkers disclosed herein are useful for the diagnosis of Alzheimer's disease, monitoring the progression of Alzheimer's disease in a subject and in screening methods for the identification of compounds for treating or preventing Alzheimer's disease. The invention is also directed to kits containing reagents for the detection and diagnosis of Alzheimer's disease using the Alzheimer's disease-specific molecular biomarkers disclosed herein.
摘要翻译：本发明涉及通过检测用蛋白激酶C激活剂刺激后细胞中特异性磷酸化MAP激酶蛋白比例的变化来诊断受试者中的阿尔茨海默氏病的方法。本文公开的阿尔茨海默氏病特异性分子生物标志物可用于诊断阿尔茨海默氏病，监测受试者中阿尔茨海默氏病的进展和用于鉴定用于治疗或预防阿尔茨海默氏病的化合物的筛选方法。本发明还涉及使用本文公开的阿尔茨海默氏病特异性分子生物标志物的含有用于检测和诊断阿尔茨海默病的试剂的试剂盒。

10. 发明申请

US20090029873A1 Alzheimer's Disease-Specific Alterations of the Erk1/Erk2 Phosphorylation Ratio-Alzheimer's Disease-Specific Molecular Biomarkers (Adsmb) 审中-公开
标题翻译： Erk1 / Erk2磷酸化比例的阿尔茨海默病特异性改变 - 阿尔茨海默病特异性分子生物标志物（Adsmb）
公开(公告)号：US20090029873A1
公开(公告)日：2009-01-29
申请号：US12083056
申请日：2006-09-25
申请人： Tapan Kumar Khan , Daniel L. Alkon
发明人： Tapan Kumar Khan , Daniel L. Alkon
IPC分类号： C40B30/06 , C12Q1/02 , C12Q1/48 , G01N33/573
CPC分类号： G01N33/6896 , G01N2333/4709 , G01N2333/912 , G01N2800/2821
摘要： The present invention relates to methods of diagnosing Alzheimer's Disease as well as to methods of confirming the presence or absence of Alzheimer's Disease in a subject. The present invention is also directed to methods of identifying a lead compound useful for the treatment of Alzheimer's Disease by contacting non-Alzheimer's cells with an amyloid beta peptide, stimulating the cells with a protein kinase C activator, contacting the cells with a test compound, and determining the value of an Alzheimer's Disease-specific molecular biomarker. The present invention is also directed to methods of diagnosing Alzheimer's Disease in a subject by detecting alterations in the ratio of specific phosphorylated MAP kinase proteins in cells after stimulation with a protein kinase C activator. The Alzheimer's Disease-specific molecular biomarkers disclosed herein are useful for the diagnosis of Alzheimer's Disease, monitoring the progression of Alzheimer's Disease in a subject and in screening methods for the identification of compounds for treating or preventing Alzheimer's Disease. The invention is also directed to kits containing reagents for the detection and diagnosis of the presence or absence of Alzheimer's Disease using the Alzheimer's Disease-specific molecular biomarkers disclosed herein.
摘要翻译：本发明涉及诊断阿尔茨海默病的方法以及确认受试者中是否存在阿尔茨海默氏病的方法。本发明还涉及通过使非阿尔茨海默病细胞与淀粉状蛋白β肽接触，用蛋白激酶C激活剂刺激细胞，使细胞与测试化合物接触来鉴定用于治疗阿尔茨海默病的铅化合物的方法，并确定阿尔茨海默氏病特异性分子生物标志物的价值。本发明还涉及通过检测用蛋白激酶C激活剂刺激后细胞中特异性磷酸化MAP激酶蛋白的比例变化来诊断受试者中的阿尔茨海默氏病的方法。本文公开的阿尔茨海默病特异性分子生物标志物可用于诊断阿尔茨海默氏病，监测受试者中阿尔茨海默氏病的进展和用于鉴定用于治疗或预防阿尔茨海默氏病的化合物的筛选方法。本发明还涉及包含用于使用本文公开的阿尔茨海默病特异性分子生物标志物来检测和诊断阿尔茨海默氏病或不存在的试剂的试剂盒。

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