公开(公告)号：US09283230B2

公开(公告)日：2016-03-15

申请号：US13984841

申请日：2011-08-15

申请人： Scott Clunas ,  John Mervyn David Storey ,  James Peter Sinclair ,  Thomas Craven Baddeley ,  Ahtsham Ishaq ,  Michael Simpson ,  Craig Williamson ,  Barry Alan Wood ,  Claude Michel Wischik ,  Charles Robert Harrington ,  Janet Elizabeth Rickard ,  David Horsley ,  Yin Sze Loh ,  Colin Marshall ,  Karrar Ahmad Khan

发明人： Scott Clunas ,  John Mervyn David Storey ,  James Peter Sinclair ,  Thomas Craven Baddeley ,  Ahtsham Ishaq ,  Michael Simpson ,  Craig Williamson ,  Barry Alan Wood ,  Claude Michel Wischik ,  Charles Robert Harrington ,  Janet Elizabeth Rickard ,  David Horsley ,  Yin Sze Loh ,  Colin Marshall ,  Karrar Ahmad Khan

IPC分类号： A61K31/5415 ,  C07D279/20 ,  C07D309/04 ,  C07C309/05 ,  A61K9/20 ,  C07C309/04 ,  A61K9/28 ,  C07C309/30 ,  C07C309/35

CPC分类号： A61K31/5415 ,  A61K9/0053 ,  A61K9/2095 ,  A61K9/2893 ,  A61L2/0052 ,  C07C303/32 ,  C07C309/04 ,  C07C309/05 ,  C07C309/30 ,  C07C309/35 ,  C07D279/20 ,  Y02A50/393 ,  Y02A50/411

摘要： The invention relates to compounds of general formula (I): wherein: each of R1 and R9 is independently selected from: —H, C1-4alkyl, C2-4alkenyl, and halogenated C1-4alkyl; each of R3NA and R3NB is independently selected from: —H, C1-4alkyl, C2-4alkenyl, and halogenated C1-4alkyl; each of R7NA and R7NB is independently selected from: —H, C1-4alkyl, C2-4alkenyl, and halogenated C1-4alkyl; and wherein: each of RA and RB is independently selected from: C1-4alkyl, halogenated C1-4alkyl, and C6-10aryl; or RA and RB are linked to form a group selected from: C1-6 alkylene and C6-10 arylene; and pharmaceutically acceptable salts thereof, which are useful in the treatment of, for example, Alzheimer's disease. In other aspects the invention also relates to novel formulations of 3,7-diamino-10H-phenothiazinium salts.

摘要翻译： 本发明涉及通式（I）的化合物：其中：R 1和R 9各自独立地选自：-H，C 1-4烷基，C 2-4链烯基和卤代C 1-4烷基; R 3NA和R 3NB中的每一个独立地选自：-H，C 1-4烷基，C 2-4链烯基和卤代C 1-4烷基; R7NA和R7NB中的每一个独立地选自：-H，C 1-4烷基，C 2-4链烯基和卤代C 1-4烷基; 并且其中：RA和RB各自独立地选自：C 1-4烷基，卤代C 1-4烷基和C 6-10芳基; 或RA和RB连接形成选自以下的基团：C 1-6亚烷基和C 6-10亚芳基; 和其药学上可接受的盐，其可用于治疗例如阿尔茨海默氏病。 在其它方面，本发明还涉及3,7-二氨基-10H-吩噻嗪鎓盐的新配方。

公开(公告)号：US20130315992A1

公开(公告)日：2013-11-28

申请号：US13984841

申请日：2011-08-15

申请人： Scott Clunas ,  John Mervyn David Storey ,  James Peter Sinclair ,  Thomas Craven Baddeley ,  Ahtsham Ishaq ,  Michael Simpson ,  Craig Williamson ,  Barry Alan Wood ,  Claude Michel Wischik ,  Charles Robert Harrington ,  Janet Elizabeth Rickard ,  David Horsley ,  Yin Sze Loh ,  Colin Marshall ,  Karrar Ahmad Khan

发明人： Scott Clunas ,  John Mervyn David Storey ,  James Peter Sinclair ,  Thomas Craven Baddeley ,  Ahtsham Ishaq ,  Michael Simpson ,  Craig Williamson ,  Barry Alan Wood ,  Claude Michel Wischik ,  Charles Robert Harrington ,  Janet Elizabeth Rickard ,  David Horsley ,  Yin Sze Loh ,  Colin Marshall ,  Karrar Ahmad Khan

IPC分类号： C07D279/20 ,  C07C309/30 ,  A61K9/28 ,  C07C309/35 ,  A61K9/20 ,  C07C309/04 ,  C07C309/05

CPC分类号： A61K31/5415 ,  A61K9/0053 ,  A61K9/2095 ,  A61K9/2893 ,  A61L2/0052 ,  C07C303/32 ,  C07C309/04 ,  C07C309/05 ,  C07C309/30 ,  C07C309/35 ,  C07D279/20 ,  Y02A50/393 ,  Y02A50/411

摘要： The invention relates to compounds of general formula (I): wherein: each of R1 and R9 is independently selected from: —H, C1-4alkyl, C2-4alkenyl, and halogenated C1-4alkyl; each of R3NA and R3NB is independently selected from: —H, C1-4alkyl, C2-4alkenyl, and halogenated C1-4alkyl; each of R7NA and R7NB is independently selected from: —H, C1-4alkyl, C2-4alkenyl, and halogenated C1-4alkyl; and wherein: each of RA and RB is independently selected from: C1-4alkyl, halogenated C1-4alkyl, and C6-10aryl; or RA and RB are linked to form a group selected from: C1-6 alkylene and C6-10 arylene; and pharmaceutically acceptable salts thereof, which are useful in the treatment of, for example, Alzheimer's disease. In other aspects the invention also relates to novel formulations of 3,7-diamino-10H-phenothiazinium salts.

摘要翻译： 本发明涉及通式（I）的化合物：其中：R 1和R 9各自独立地选自：-H，C 1-4烷基，C 2-4链烯基和卤代C 1-4烷基; R 3NA和R 3NB中的每一个独立地选自：-H，C 1-4烷基，C 2-4链烯基和卤代C 1-4烷基; R7NA和R7NB中的每一个独立地选自：-H，C 1-4烷基，C 2-4链烯基和卤代C 1-4烷基; 并且其中：RA和RB各自独立地选自：C 1-4烷基，卤代C 1-4烷基和C 6-10芳基; 或RA和RB连接形成选自以下的基团：C 1-6亚烷基和C 6-10亚芳基; 和其药学上可接受的盐，其可用于治疗例如阿尔茨海默氏病。 在其它方面，本发明还涉及3,7-二氨基-10H-吩噻嗪鎓盐的新配方。

公开(公告)号：US07888350B2

公开(公告)日：2011-02-15

申请号：US12294599

申请日：2007-03-28

申请人： Claude Michel Wischik ,  Janet Elizabeth Rickard ,  Charles Robert Harrington ,  David Horsley ,  John Mervyn David Storey ,  Colin Marshall ,  James Peter Sinclair ,  Thomas Craven Baddeley

发明人： Claude Michel Wischik ,  Janet Elizabeth Rickard ,  Charles Robert Harrington ,  David Horsley ,  John Mervyn David Storey ,  Colin Marshall ,  James Peter Sinclair ,  Thomas Craven Baddeley

IPC分类号： C07D279/18 ,  A61K31/5415

CPC分类号： A61K31/5415 ,  C07D279/20 ,  C07D279/22 ,  C09B21/00 ,  Y02A50/393 ,  Y02A50/411

摘要： This invention pertains generally to the field of phenothiazine compounds, and more particularly to certain stably reduced phenothiazine compounds, specifically, certain 3,7 diamino-10H-phenothiazine (DAPTZ) compounds of the following formula wherein: each of R1 and R9 is independently selected from: —H; C1-4alkyl; C2-4alkenyl; and halogenated C1-4alkyl; each of R3NA and R3NB is independently selected from: —H; C1-4alkyl; C2-4alkenyl; and halogenated C1-4alkyl; each of R7NA and R7NB is independently selected from: —H; C1-4alkyl; C2-4alkenyl; and halogenated C1-4alkyl; each of HX1 and HX2 is independently a protic acid; and pharmaceutically acceptable salts, solvates, and hydrates thereof. These compounds are useful as drugs, for example, in the treatment of tauopathies, such as Alzheimer's disease, and also as prodrugs for the corresponding oxidized thioninium drugs (for example, methythioninium chloride, MTC).

摘要翻译： 本发明一般涉及吩噻嗪化合物领域，更具体地涉及某些稳定还原的吩噻嗪化合物，具体地，下列通式的某些3,7-二氨基-10H-吩噻嗪（DAPTZ）化合物其中：R 1和R 9各自独立地选自 从：-H; C 1-4烷基; C2-4烯基; 和卤代C 1-4烷基; R3NA和R3NB中的每一个独立地选自：-H; C 1-4烷基; C2-4烯基; 和卤代C 1-4烷基; R7NA和R7NB中的每一个独立地选自：-H; C 1-4烷基; C2-4烯基; 和卤代C 1-4烷基; HX1和HX2各自独立地是质子酸; 及其药学上可接受的盐，溶剂化物和水合物。 这些化合物可用作药物，例如用于治疗tau蛋白病如阿尔茨海默氏病，以及作为相应的氧化硫堇药物（例如氯化甲硫氨酸，MTC）的前药。

公开(公告)号：US08710051B2

公开(公告)日：2014-04-29

申请号：US13011797

申请日：2011-01-21

申请人： Claude Michel Wischik ,  Janet Elizabeth Rickard ,  Charles Robert Harrington ,  David Horsley ,  John Mervyn David Storey ,  Colin Marshall ,  James Peter Sinclair ,  Thomas Craven Baddeley

发明人： Claude Michel Wischik ,  Janet Elizabeth Rickard ,  Charles Robert Harrington ,  David Horsley ,  John Mervyn David Storey ,  Colin Marshall ,  James Peter Sinclair ,  Thomas Craven Baddeley

IPC分类号： A61K31/54 ,  C07D279/18

CPC分类号： C07D279/20 ,  A61K31/5415 ,  A61K49/0002 ,  A61K49/003 ,  A61K51/0465 ,  G01N33/6896 ,  G01N2800/2835 ,  Y02A50/393 ,  Y02A50/411

摘要： This invention pertains generally to the field of phenothiazine compounds, and more particularly to certain stably reduced phenothiazine compounds, specifically, certain 3,7-diamino-10H-phenothiazine (DAPTZ) compounds of the following formula: wherein: each of R1 and R9 is independently selected from: —H; C1-4alkyl; C2-4alkenyl; and halogenated C1-4alkyl; each of R3NA and R3NB is independently selected from: —H; C1-4alkyl; C2-4alkenyl; and halogenated C1-4alkyl; each of R7NA and R7NB is independently selected from: —H; C1-4alkyl; C2-4alkenyl; and halogenated C1-4alkyl; each of HX1 and HX2 is independently a protic acid; and pharmaceutically acceptable salts, solvates, and hydrates thereof. These compounds are useful as drugs, for example, in the treatment of tauopathies, such as Alzheimer's disease, and also as prodrugs for the corresponding oxidized thioninium drugs (for example, methylthioninium chloride, MTC).

摘要翻译： 本发明一般涉及吩噻嗪化合物领域，更具体地涉及某些稳定还原的吩噻嗪化合物，具体地，下列通式的某些3,7-二氨基-10H-吩噻嗪（DAPTZ）化合物：其中：R 1和R 9各自为 独立选自：-H; C 1-4烷基; C2-4烯基; 和卤代C 1-4烷基; R3NA和R3NB中的每一个独立地选自：-H; C 1-4烷基; C2-4烯基; 和卤代C 1-4烷基; R7NA和R7NB中的每一个独立地选自：-H; C 1-4烷基; C2-4烯基; 和卤代C 1-4烷基; HX1和HX2各自独立地是质子酸; 及其药学上可接受的盐，溶剂化物和水合物。 这些化合物可用作药物，例如用于治疗tau蛋白病，例如阿尔茨海默氏病，以及作为相应的氧化硫堇药物（例如，甲基硫堇，MTC）的前药。

公开(公告)号：US20110118242A1

公开(公告)日：2011-05-19

申请号：US13011797

申请日：2011-01-21

申请人： Claude Michel WISCHIK ,  Janet Elizabeth Rickard ,  Charles Robert Harrington ,  David Horsley ,  John Mervyn David Storey ,  Colin Marshall ,  James Peter Sinclair ,  Thomas Craven Baddeley

发明人： Claude Michel WISCHIK ,  Janet Elizabeth Rickard ,  Charles Robert Harrington ,  David Horsley ,  John Mervyn David Storey ,  Colin Marshall ,  James Peter Sinclair ,  Thomas Craven Baddeley

IPC分类号： A61K31/5415 ,  A61P25/28

CPC分类号： C07D279/20 ,  A61K31/5415 ,  A61K49/0002 ,  A61K49/003 ,  A61K51/0465 ,  G01N33/6896 ,  G01N2800/2835 ,  Y02A50/393 ,  Y02A50/411

摘要： This invention pertains generally to the field of phenothiazine compounds, and more particularly to certain stably reduced phenothiazine compounds, specifically, certain 3,7-diamino-10H-phenothiazine (DAPTZ) compounds of the following formula: wherein: each of R1 and R9 is independently selected from: —H; C1-4alkyl; C2-4alkenyl; and halogenated C1-4alkyl; each of R3NA and R3NB is independently selected from: —H; C1-4alkyl; C2-4alkenyl; and halogenated C1-4alkyl; each of R7NA and R7NB is independently selected from: —H; C1-4alkyl; C2-4alkenyl; and halogenated C1-4alkyl; each of HX1 and HX2 is independently a protic acid; and pharmaceutically acceptable salts, solvates, and hydrates thereof. These compounds are useful as drugs, for example, in the treatment of tauopathies, such as Alzheimer's disease, and also as prodrugs for the corresponding oxidized thioninium drugs (for example, methylthioninium chloride, MTC).

摘要翻译： 本发明一般涉及吩噻嗪化合物领域，更具体地涉及某些稳定还原的吩噻嗪化合物，具体地，下列通式的某些3,7-二氨基-10H-吩噻嗪（DAPTZ）化合物：其中：R 1和R 9各自为 独立选自：-H; C 1-4烷基; C2-4烯基; 和卤代C 1-4烷基; R3NA和R3NB中的每一个独立地选自：-H; C 1-4烷基; C2-4烯基; 和卤代C 1-4烷基; R7NA和R7NB中的每一个独立地选自：-H; C 1-4烷基; C2-4烯基; 和卤代C 1-4烷基; HX1和HX2各自独立地是质子酸; 及其药学上可接受的盐，溶剂化物和水合物。 这些化合物可用作药物，例如用于治疗tau蛋白病，例如阿尔茨海默氏病，以及作为相应的氧化硫堇药物（例如，甲基硫堇，MTC）的前药。

公开(公告)号：US20090054419A1

公开(公告)日：2009-02-26

申请号：US12294599

申请日：2007-03-28

申请人： Claude Michel Wischik ,  Janet Elizabeth Rickard ,  Charles Robert Harrington ,  David Horsley ,  John Mervyn David Storey ,  Colin Marshall ,  James Peter Sinclair ,  Thomas Craven Baddeley

发明人： Claude Michel Wischik ,  Janet Elizabeth Rickard ,  Charles Robert Harrington ,  David Horsley ,  John Mervyn David Storey ,  Colin Marshall ,  James Peter Sinclair ,  Thomas Craven Baddeley

IPC分类号： A61K31/5415 ,  C07D279/30 ,  C07D279/20 ,  C07K1/113

CPC分类号： A61K31/5415 ,  C07D279/20 ,  C07D279/22 ,  C09B21/00 ,  Y02A50/393 ,  Y02A50/411

摘要： This invention pertains generally to the field of phenothiazine compounds, and more particularly to certain stably reduced phenothiazine compounds, specifically, certain 3,7 diamino-10H-phenothiazine (DAPTZ) compounds of the following formula wherein: each of R1 and R9 is independently selected from: —H; C1-4alkyl; C2-4alkenyl; and halogenated C1-4alkyl; each of R3NA and R3NB is independently selected from: —H; C1-4alkyl; C2-4alkenyl; and halogenated C1-4alkyl; each of R7NA and R7NB is independently selected from: —H; C1-4alkyl; C2-4alkenyl; and halogenated C1-4alkyl; each of HX1 and HX2 is independently a protic acid; and pharmaceutically acceptable salts, solvates, and hydrates thereof. These compounds are useful as drugs, for example, in the treatment of tauopathies, such as Alzheimer's disease, and also as prodrugs for the corresponding oxidized thioninium drugs (for example, methythioninium chloride, MTC).

摘要翻译： 本发明一般涉及吩噻嗪化合物领域，更具体地涉及某些稳定还原的吩噻嗪化合物，具体地，下列通式的某些3,7-二氨基-10H-吩噻嗪（DAPTZ）化合物其中：R 1和R 9各自独立地选自 从：-H; C 1-4烷基; C2-4烯基; 和卤代C 1-4烷基; R3NA和R3NB中的每一个独立地选自：-H; C 1-4烷基; C2-4烯基; 和卤代C 1-4烷基; R7NA和R7NB中的每一个独立地选自：-H; C 1-4烷基; C2-4烯基; 和卤代C 1-4烷基; HX1和HX2各自独立地是质子酸; 及其药学上可接受的盐，溶剂化物和水合物。 这些化合物可用作药物，例如用于治疗tau蛋白病如阿尔茨海默氏病，以及作为相应的氧化硫堇药物（例如氯化甲硫氨酸，MTC）的前药。

公开(公告)号：US20110300074A1

公开(公告)日：2011-12-08

申请号：US13133868

申请日：2009-12-10

申请人： Scott Clunas ,  John Mervyn David Storey ,  Janet Elizabeth Rickard ,  David Horsley ,  Charles Robert Harrington ,  Claude Michel Wischik

发明人： Scott Clunas ,  John Mervyn David Storey ,  Janet Elizabeth Rickard ,  David Horsley ,  Charles Robert Harrington ,  Claude Michel Wischik

IPC分类号： A61K49/00 ,  A61K31/352 ,  A61K31/5377 ,  A61K31/4545 ,  A61K31/4025 ,  A61K31/382 ,  A61K31/498 ,  A61K31/538 ,  A61P25/28 ,  A61P25/16 ,  A61P25/00 ,  C07K14/00 ,  G01N33/566 ,  C07D491/22 ,  C07D311/82 ,  C07D335/10 ,  C07D413/14 ,  C07D405/14 ,  C07D241/46 ,  C07D265/38 ,  C07D493/16 ,  G01N33/53 ,  A61K31/4375

CPC分类号： C07D311/82 ,  A61K9/0053 ,  A61K31/352 ,  A61K31/382 ,  A61K31/4025 ,  A61K31/4545 ,  A61K31/4745 ,  A61K31/498 ,  A61K31/5377 ,  A61K31/538 ,  A61K45/06 ,  A61K49/00 ,  C07D241/46 ,  C07D265/38 ,  C07D311/84 ,  C07D311/90 ,  C07D335/12 ,  C07D335/14 ,  C07D335/20 ,  C07D491/16 ,  C07D491/22 ,  C07D493/16 ,  C09B11/24 ,  C09B11/28 ,  C09B17/00 ,  C09B19/00 ,  C09B21/00 ,  C09B57/00 ,  G01N33/6896 ,  G01N2800/7047

摘要： This invention pertains generally to processes, uses, methods and materials utilising particular xanthylium compounds, including compounds of formula (I) and (II), as further defined herein. These compounds are useful as drugs, for example, in the treatment of tauopathies, such as Alzheimer's disease.

摘要翻译： 本发明一般涉及使用特定的呫吨化合物（包括式（I）和（II）的化合物）的方法，用途，方法和材料，如本文进一步定义。 这些化合物可用作药物，例如用于治疗tau蛋白病如阿尔茨海默氏病。

公开(公告)号：US08658665B2

公开(公告)日：2014-02-25

申请号：US13133868

申请日：2009-12-10

申请人： Scott Clunas ,  John Mervyn David Storey ,  Janet Elizabeth Rickard ,  David Horsley ,  Charles Robert Harrington ,  Claude Michel Wischik

发明人： Scott Clunas ,  John Mervyn David Storey ,  Janet Elizabeth Rickard ,  David Horsley ,  Charles Robert Harrington ,  Claude Michel Wischik

IPC分类号： A61K31/44 ,  C07D491/00

CPC分类号： C07D311/82 ,  A61K9/0053 ,  A61K31/352 ,  A61K31/382 ,  A61K31/4025 ,  A61K31/4545 ,  A61K31/4745 ,  A61K31/498 ,  A61K31/5377 ,  A61K31/538 ,  A61K45/06 ,  A61K49/00 ,  C07D241/46 ,  C07D265/38 ,  C07D311/84 ,  C07D311/90 ,  C07D335/12 ,  C07D335/14 ,  C07D335/20 ,  C07D491/16 ,  C07D491/22 ,  C07D493/16 ,  C09B11/24 ,  C09B11/28 ,  C09B17/00 ,  C09B19/00 ,  C09B21/00 ,  C09B57/00 ,  G01N33/6896 ,  G01N2800/7047

摘要： This invention pertains generally to processes, uses, methods and materials utilizing particular xanthylium compounds, including compounds of formula (I) and (II), as further defined herein. These compounds are useful as drugs, for example, in the treatment of tauopathies, such as Alzheimer's disease.

摘要翻译： 本发明一般涉及使用特定的呫吨化合物（包括式（I）和（II）的化合物）的方法，用途，方法和材料，如本文进一步定义。 这些化合物可用作药物，例如用于治疗tau蛋白病如阿尔茨海默氏病。

公开(公告)号：US08895313B2

公开(公告)日：2014-11-25

申请号：US13063525

申请日：2009-09-23

申请人： Steven John Kemp ,  Lynda Jane Storey ,  John Mervyn David Storey ,  Janet Rickard ,  Charles Robert Harrington ,  Claude Michel Wischik ,  Scott Clunas ,  Tobias Kerst Heinrich

发明人： Steven John Kemp ,  Lynda Jane Storey ,  John Mervyn David Storey ,  Janet Rickard ,  Charles Robert Harrington ,  Claude Michel Wischik ,  Scott Clunas ,  Tobias Kerst Heinrich

IPC分类号： G01N33/50 ,  C07D277/66 ,  C07D417/12 ,  C07D513/04 ,  C07D471/04 ,  C07D487/04 ,  G01N33/68

CPC分类号： G01N33/6896 ,  C07D277/66 ,  C07D417/12 ,  C07D471/04 ,  C07D487/04 ,  C07D513/04 ,  G01N2333/4709 ,  G01N2800/2821 ,  Y10T436/14 ,  Y10T436/147777 ,  Y10T436/17 ,  Y10T436/18

摘要： Provided are certain benzothiazole, imidazothiazole, imidazopyrimidine and imidazopyridine compounds, including, for example: formula (I) and pharmaceutically and physiologically acceptable salts, hydrates, and solvates thereof. Such compounds can be used as diagnostic ligands or labels of tau protein and PHF.

摘要翻译： 提供某些苯并噻唑，咪唑并噻唑，咪唑并嘧啶和咪唑并吡啶化合物，包括例如：式（I）及其药学上和生理上可接受的盐，水合物和溶剂化物。 此类化合物可用作tau蛋白和PHF的诊断配体或标记。

公开(公告)号：US07335652B2

公开(公告)日：2008-02-26

申请号：US10665008

申请日：2003-09-22

申请人： Claude Michel Wischik ,  Charles Robert Harrington ,  Janet Elizabeth Rickard ,  David Horsley

发明人： Claude Michel Wischik ,  Charles Robert Harrington ,  Janet Elizabeth Rickard ,  David Horsley

IPC分类号： A61K31/54

CPC分类号： C07D417/12 ,  C07D277/66 ,  C07D279/20 ,  G01N33/583 ,  G01N33/6896

摘要： Disclosed are methods for determining the stage of neurofibrillary degeneration associated with a tauopathy in a subject believed to suffer from the disease, by (i) introducing into the subject a ligand capable of labeling aggregated paired helical filament (PHF) tau protein, (ii) determining the presence and/or amount of ligand bound to extracellular aggregated PHF tau in the medial temporal lobe of the brain of the subject, (iii) correlating the result of the determination made in (ii) with the extent of neurofibrillary degeneration in the subject. The methods can be used for pre-mortem diagnosis and staging of tauopathies such as Alzheimer's Disease. Preferred ligands include sulphonated-benzothiazole-like compounds and diaminophenothiazines.

摘要翻译： 公开了用于确定被认为患有疾病的受试者中与tau蛋白病相关的神经原纤维变性的阶段的方法，方法是（i）向受试者引入能够标记聚集的成对螺旋丝（PHF）tau蛋白的配体，（ii） 确定与受试者的脑内侧颞叶结合的细胞外聚集的PHF tau的配体的存在和/或量的量，（iii）将（ii）中确定的测定结果与受试者的神经原纤维变性程度相关联 。 这些方法可用于妊娠前诊断和分期的阿尔茨海默病等tau蛋白病。 优选的配体包括磺化苯并噻唑类化合物和二氨基吩噻嗪。