Search

EP-4739799-A1 - A METHOD FOR AN IN VITRO DIAGNOSIS, PROGNOSIS, STAGING AND/OR TREATMENT MONITORING OF A NEURODEGENERATIVE DISEASE, NEUROLOGICAL DISEASE OR AMYLOID BETA-RELATED DISEASE

EP4739799A1EP 4739799 A1EP4739799 A1EP 4739799A1EP-4739799-A1

Abstract

The invention relates to a method for an in vitro diagnosis, prognosis, staging and/or treatment monitoring of a neurodegenerative disease, neurological disease or amyloid β-related disease. The invention further relates to a kit for performing the present method.

Inventors

  • MAMEDE FIGUEIREDO, Ricardo
  • HOFFMEIER, Klaus
  • ROTTER, Björn

Assignees

  • Genxpro GmbH

Dates

Publication Date
20260513
Application Date
20230707

Claims (20)

  1. 1 . A method for an in vitro diagnosis, prognosis, staging and/or treatment monitoring of a neurodegenerative disease, neurological disease or amyloid [3- related disease, wherein the method comprises the steps: a) Obtaining an RNA sample from at least one biological fluid obtained from an individual; b) Determining an expression level of at least one predetermined RNA based on the RNA sample obtained in step a); c) Comparing said expression level to one or several reference expression levels, wherein the comparison of said determined expression level to said one or several reference expression levels is used for the diagnosis, prognosis, staging and/or treatment monitoring of the disease; wherein said at least one predetermined RNA is selected from the group consisting of Fxyd3, Trappc3, Clstn2, Deptor, Hoxaas3, Sdk1 , Gm42836, Ldb2, Hist1 h3c, 201001611 SRik, 5430405H02Rik, AC160051.3, Mrpl45, Slc9a9, 5031415H12Rik, Gm12940, Gm20628, AC131120.1 , Gm20634, 4930512B01 Rik, Hist2h2be, Gm43581 , A430018G15Rik, Gm43062, mmu-miR- 216a-5p, B930095G15Rik, Gm20501 , CT033754.1 , Pou2af1 , Reps2, Hist1 h4b, Gm26699, Gm19409, Pld5, Gm16105, 9330160F10Rik, B230398E01 Rik, Gm44633, CT030159.2, Eif4g3, Gm44570, Gm31718, Nr6a1 os, Tmem250-ps, 8430423G03Rik, D930016D06Rik, Slc4a7, Gm26831 , AC165261.1 , A430072P03Rik, Gm7331 , Gm 12374, Gm 15832, C030029H02Rik, Adamts2, 4930509H03Rik, Tex50, 4930556M19Rik; D830025C05Rik, AC117194.1 , 4732496C06Rik, Gm32122, Gm42303, Gm45609, Gm45733, Gm37401 , Gm43112, Gm 14703, AC153506.3, EU599041 , Gm20342, A430010J10Rik, 4930488L21 Rik, Gm42939, A430010J10Rik, Arhgef16, Mir124-2hg, AA465934, Gm29325, C230088H06Rik, Kcnq1 ot1 , Gm43696, AC121793.2, Rrnadl , AC151971.9, Gm19656, 5830416119Rik, Gm28707, CT010463.2, AI849053, Gm43972, Gm5431 , 4930452N14Rik, Gm13568, Gm13055, Gm26909, Gm45379, Gm 10062, 9430065F17Rik, Plcbl , PlatrW, Gm20644, Gm21986, 9430065F17Rik, Gm26632, Wbscr25, Dbpht2, Hist2h4, Gm11131 , Wbscr25, Sncaip, Adap2os, Gm44115, Sortl , Tug1 , Colgalt2, Scrnl ; and Pou2af1 , 2010016118Rik, A430072P03Rik, Arhgef16, Gm12374, Gm43581 , Gm5431 , 9330160F10Rik, PlatrW, Gm21986, Gm26632, 5031415H12Rik, Mrpl45, Reps2, Sncaip, Tug1 , Gm43062, Scrnl , AC165261.1 , Eif4g3, Gm7331.
  2. 2. The method according to claim 1 , wherein said at least one predetermined RNA is selected from the group consisting of Fxyd3 (ST), Trappc3 (ST), Clstn2 (AS), Deptor (AS), Hoxaas3 (ST), Sdk1 (ST), Gm42836 (ST), Ldb2 (AS), Hist1 h3c (ST), 2010016118Rik (AS), 5430405H02Rik (ST), AC160051.3 (ST), Mrpl45 (AS), Slc9a9 (ST), 5031415H12Rik (AS), Gm12940 (ST), Gm20628 (ST), AC131120.1 (ST), Gm20634 (ST), 4930512B01 Rik (ST), Hist2h2be (ST), Gm43581 (AS), A430018G15Rik (ST), Gm43062 (AS), mmu-miR-216a-5p (ST), B930095G15Rik (ST), Gm20501 (ST), CT033754.1 (ST), Pou2af1 (AS), Reps2 (ST), Hist1 h4b (ST), Gm26699 (ST), Gm 19409 (ST), Pld5 (AS), Gm 16105 (ST), 9330160F10Rik (AS), B230398E01 Rik (ST), Gm44633 (ST), CT030159.2 (ST), Eif4g3 (ST), Gm44570 (ST), Gm31718 (ST), Nr6a1 os (ST), Tmem250-ps (ST), 8430423G03Rik (ST), D930016D06Rik (ST), Slc4a7 (ST), Gm26831 (ST), AC165261.1 (AS), A430072P03Rik (AS), Gm7331 (AS), Gm12374 (AS), Gm15832 (ST), C030029H02Rik (ST), Adamts2 (ST), 4930509H03Rik (ST), Tex50 (ST), 4930556M19Rik (ST); D830025C05Rik (ST), AC117194.1 (ST), 4732496C06Rik (ST), Gm32122 (ST), Gm42303 (ST), Gm45609 (ST), Gm45733 (ST), Gm37401 (ST), Gm43112 (ST), Gm 14703 (ST), AC153506.3 (ST), EU599041 (ST), Gm20342 (ST), A430010J10Rik (ST), 4930488L21 Rik (ST), Gm42939 (ST), A430010J10Rik (ST), ArhgefW (AS), Mir124-2hg (ST), AA465934 (ST), Gm29325 (ST), C230088H06Rik (ST), Kcnq1 ot1 (ST), Gm43696 (ST), AC121793.2 (ST), Rrnadl (ST), AC151971.9 (ST), Gm19656 (ST), 5830416119Rik (ST), Gm28707 (ST), CT010463.2 (ST), AI849053 (ST), Gm43972 (ST), Gm5431 (AS), 4930452N14Rik (ST), Gm13568 (ST), Gm13055 (ST), Gm26909 (ST), Gm45379 (ST), Gm 10062 (ST), 9430065F17Rik (ST), Plcbl (ST), PlatrlO (ST), Gm20644 (ST), Gm21986 (ST), 9430065F17Rik (ST), Gm26632 (ST), Wbscr25 (ST), Dbpht2 (ST), Hist2h4 (ST), Gm11131 (ST), Wbscr25 (ST), Sncaip (ST), Adap2os (ST), Gm44115 (ST), Sortl (ST), Tug1 (ST), Colgalt2 (AS), Scrnl (AS); and Pou2af1 (ST), 2010016118Rik (ST), A430072P03Rik (ST), Arhgef16 (AS), Gm12374 (ST), Gm43581 (ST), Gm5431 (AS), 9330160F10Rik (ST), PlatrlO (ST), Gm21986 (ST), Gm26632 (ST), 5031415H12Rik (ST), Mrpl45 (ST), Reps2 (AS), Sncaip (ST), Tug1 (ST), Gm43062 (ST), Scrnl (AS), AC165261.1 (ST), Eif4g3 (AS), Gm7331 (ST).
  3. 3. The method according to claim 1 or 2, wherein said at least one predetermined RNA is selected from the group consisting of SEQ_NO_1 to SEQ_NO_117.
  4. 4. The method according to one of claims 1 to 3, wherein said method comprises the steps: a) Obtaining an RNA sample from at least one biological fluid obtained from an individual; b) Determining a pattern of expression levels of at least two predetermined RNAs based on the RNA sample obtained in step a); c) Comparing said pattern of expression levels to one or several reference pattern of expression levels, wherein the comparison of said determined pattern of expression levels to said one or several reference pattern of expression levels is used for the diagnosis, prognosis, staging and/or treatment monitoring of the disease; wherein said at least two predetermined RNAs are selected from the group consisting of Fxyd3, Trappc3, Clstn2, Deptor, Hoxaas3, Sdk1 , Gm42836, Ldb2, Hist1 h3c, 2010016118Rik, 5430405H02Rik, AC160051.3, Mrpl45, Slc9a9, 5031415H 12Rik, Gm12940, Gm20628, AC131120.1 , Gm20634, 4930512B01 Rik, Hist2h2be, Gm43581 , A430018G15Rik, Gm43062, mmu-miR- 216a-5p, B930095G15Rik, Gm20501 , CT033754.1 , Pou2af1 , Reps2, Hist1 h4b, Gm26699, Gm19409, Pld5, Gm16105, 9330160F10Rik, B230398E01 Rik, Gm44633, CT030159.2, Eif4g3, Gm44570, Gm31718, Nr6a1 os, Tmem250-ps, 8430423G03Rik, D930016D06Rik, Slc4a7, Gm26831 , AC165261.1 , A430072P03Rik, Gm7331 , Gm 12374, Gm 15832, C030029H02Rik, Adamts2, 4930509H03Rik, Tex50, 4930556M19Rik; D830025C05Rik, AC117194.1 , 4732496C06Rik, Gm32122, Gm42303, Gm45609, Gm45733, Gm37401 , Gm43112, Gm 14703, AC153506.3, EU599041 , Gm20342, A430010J10Rik, 4930488L21 Rik, Gm42939, A430010J10Rik, Arhgef16, Mir124-2hg, AA465934, Gm29325, C230088H06Rik, Kcnq1ot1 , Gm43696, AC121793.2, Rrnadl , AC151971.9, Gm19656, 5830416119Rik, Gm28707, CT010463.2, AI849053, Gm43972, Gm5431 , 4930452N14Rik, Gm13568, Gm13055, Gm26909, Gm45379, Gm10062, 9430065F17Rik, Plcbl , PlatrW, Gm20644, Gm21986, 9430065F17Rik, Gm26632, Wbscr25, Dbpht2, Hist2h4, Gm11131 , Wbscr25, Sncaip, Adap2os, Gm44115, Sortl , Tug1 , Colgalt2, Scrnl ; and Pou2af1 , 2010016118Rik, A430072P03Rik, Arhgef16, Gm12374, Gm43581 , Gm5431 , 9330160F10Rik, PlatrW, Gm21986, Gm26632, 5031415H12Rik, Mrpl45, Reps2, Sncaip, Tug1 , Gm43062, Scrnl , AC165261.1 , Eif4g3, Gm7331.
  5. 5. The method according to claim 4, wherein said at least two predetermined RNAs are selected from the group consisting of Fxyd3 (ST), Trappc3 (ST), Clstn2 (AS), Deptor (AS), Hoxaas3 (ST), Sdk1 (ST), Gm42836 (ST), Ldb2 (AS), Hist1 h3c (ST), 2010016118Rik (AS), 5430405H02Rik (ST), AC160051.3 (ST), Mrpl45 (AS), Slc9a9 (ST), 5031415H12Rik (AS), Gm12940 (ST), Gm20628 (ST), AC131120.1 (ST), Gm20634 (ST), 4930512B01 Rik (ST), Hist2h2be (ST), Gm43581 (AS), A430018G15Rik (ST), Gm43062 (AS), mmu-miR-216a-5p (ST), B930095G15Rik (ST), Gm20501 (ST), CT033754.1 (ST), Pou2af1 (AS), Reps2 (ST), Hist1 h4b (ST), Gm26699 (ST), Gm 19409 (ST), Pld5 (AS), Gm 16105 (ST), 9330160F10Rik (AS), B230398E01 Rik (ST), Gm44633 (ST), CT030159.2 (ST), Eif4g3 (ST), Gm44570 (ST), Gm31718 (ST), Nr6a1os (ST), Tmem250-ps (ST), 8430423G03Rik (ST), D930016D06Rik (ST), Slc4a7 (ST), Gm26831 (ST), AC165261.1 (AS), A430072P03Rik (AS), Gm7331 (AS), Gm12374 (AS), Gm 15832 (ST), C030029H02Rik (ST), Adamts2 (ST), 4930509H03Rik (ST), Tex50 (ST), 4930556M19Rik (ST); D830025C05Rik (ST), AC117194.1 (ST), 4732496C06Rik (ST), Gm32122 (ST), Gm42303 (ST), Gm45609 (ST), Gm45733 (ST), Gm37401 (ST), Gm43112 (ST), Gm 14703 (ST), AC153506.3 (ST), EU599041 (ST), Gm20342 (ST), A430010J10Rik (ST), 4930488L21 Rik (ST), Gm42939 (ST), A430010J10Rik (ST), Arhgef16 (AS), Mir124-2hg (ST), AA465934 (ST), Gm29325 (ST), C230088H06Rik (ST), Kcnq1ot1 (ST), Gm43696 (ST), AC121793.2 (ST), Rrnadl (ST), AC151971.9 (ST), Gm19656 (ST), 5830416119Rik (ST), Gm28707 (ST), CT010463.2 (ST), AI849053 (ST), Gm43972 (ST), Gm5431 (AS), 4930452N14Rik (ST), Gm13568 (ST), Gm13055 (ST), Gm26909 (ST), Gm45379 (ST), Gm 10062 (ST), 9430065F17Rik (ST), Plcbl (ST), PlatrlO (ST), Gm20644 (ST), Gm21986 (ST), 9430065F17Rik (ST), Gm26632 (ST), Wbscr25 (ST), Dbpht2 (ST), Hist2h4 (ST), Gm11131 (ST), Wbscr25 (ST), Sncaip (ST), Adap2os (ST), Gm44115 (ST), Sortl (ST), Tug1 (ST), Colgalt2 (AS), Scrnl (AS); and Pou2af1 (ST), 2010016118Rik (ST), A430072P03Rik (ST), Arhgef16 (AS), Gm12374 (ST), Gm43581 (ST), Gm5431 (AS), 9330160F10Rik (ST), PlatrlO (ST), Gm21986 (ST), Gm26632 (ST), 5031415H12Rik (ST), Mrpl45 (ST), Reps2 (AS), Sncaip (ST), Tug1 (ST), Gm43062 (ST), Scrnl (AS), AC165261.1 (ST), Eif4g3 (AS), Gm7331 (ST); or wherein said at least two predetermined RNAs are selected from the group consisting of SEQ_NO_1 to SEQ_NO_117.
  6. 6. The method according to one of claims 1 to 5, wherein the neurodegenerative disease, neurological disease or amyloid [3-related disease is Alzheimer's Disease.
  7. 7. The method according to one of claims 1 to 6, wherein said expression level or said pattern of expression levels is determined of at least one predetermined RNA or at least three predetermined RNAs selected from the group consisting of D830025C05Rik, AC117194.1 , 4732496C06Rik, Gm32122, Gm42303, Gm45609, Gm45733, Gm37401 , Gm43112, Gm 14703, AC153506.3, EU599041 , Gm20342, A430010J10Rik, 4930488L21 Rik, Gm42939, A430010J10Rik, Arhgef16, Mir124-2hg, AA465934, Gm29325, C230088H06Rik, Kcnq1 ot1 , Gm43696, AC121793.2, Rrnadl , AC151971.9, Gm19656, 5830416119Rik, Gm28707, CT010463.2, AI849053, Gm43972, Gm5431 , 4930452N14Rik, Gm13568, Gm13055, Gm26909, Gm45379, Gm10062, 9430065F17Rik, Plcbl , PlatrW, Gm20644, Gm21986, 9430065F17Rik, Gm26632, Wbscr25, Dbpht2, Hist2h4, Gm11131 , Wbscr25, Sncaip, Adap2os, Gm44115, Sortl , Tug1 , Colgalt2, Scrnl .
  8. 8. The method of claim 7, wherein said expression level or said pattern of expression levels is determined of at least one predetermined RNA or at least three predetermined RNAs selected from the group consisting of D830025C05Rik (ST), AC117194.1 (ST), 4732496C06Rik (ST), Gm32122 (ST), Gm42303 (ST), Gm45609 (ST), Gm45733 (ST), Gm37401 (ST), Gm43112 (ST), Gm 14703 (ST), AC153506.3 (ST), EU599041 (ST), Gm20342 (ST), A430010J10Rik (ST), 4930488L21 Rik (ST), Gm42939 (ST), A430010J10Rik (ST), ArhgefW (AS), Mir124-2hg (ST), AA465934 (ST), Gm29325 (ST), C230088H06Rik (ST), Kcnq1 ot1 (ST), Gm43696 (ST), AC121793.2 (ST), Rrnadl (ST), AC151971 .9 (ST), Gm19656 (ST), 5830416119Rik (ST), Gm28707 (ST), CT010463.2 (ST), AI849053 (ST), Gm43972 (ST), Gm5431 (AS), 4930452N14Rik (ST), Gm13568 (ST), Gm13055 (ST), Gm26909 (ST), Gm45379 (ST), Gm 10062 (ST), 9430065F17Rik (ST), Plcbl (ST), PlatrW (ST), Gm20644 (ST), Gm21986 (ST), 9430065F17Rik (ST), Gm26632 (ST), Wbscr25 (ST), Dbpht2 (ST), Hist2h4 (ST), Gm11131 (ST), Wbscr25 (ST), Sncaip (ST), Adap2os (ST), Gm44115 (ST), Sortl (ST), Tug1 (ST), Colgalt2 (AS), Scrnl (AS); or wherein said expression level or said pattern of expression levels is determined of at least one predetermined RNA or at least three predetermined RNAs selected from the group consisting of SEQ_NO_22, SEQ_NO_23, SEQ_NO_24, SEQ_NO_25, SEQ_NO_26, SEQ_NO_27, SEQ_NO_28, SEQ_NO_29, SEQ_NO_30, SEQ_NO_31 , SEQ_NO_32, SEQ_NO_33, SEQ_NO_34, SEQ_NO_35, SEQ_NO_36, SEQ_NO_37, SEQ_NO_38, SEQ_NO_4, SEQ_NO_39, SEQ_NO_40, SEQ_NO_41 , SEQ_NO_42, SEQ_NO_43, SEQ_NO_44, SEQ_NO_45, SEQ_NO_46, SEQ_NO_47, SEQ_NO_48, SEQ_NO_49, SEQ_NO_50, SEQ_NO_51 , SEQ_NO_52, SEQ_NO_53, SEQ_NO_7, SEQ_NO_54, SEQ_NO_55, SEQ_NO_56, SEQ_NO_57, SEQ_NO_58, SEQ_NO_59, SEQ_NO_60, SEQ_NO_61 , SEQ_NO_09, SEQ_NO_62, SEQ_NO_10 SEQ_NO_63, SEQ_NO_64, SEQ_NO_65, SEQ_NO_66, SEQ_NO_67, SEQ_NO_68, SEQ_NO_15, SEQ_NO_69, SEQ_NO_70, SEQ_NO_71 , SEQ_NO_16, SEQ_NO_72, SEQ_NO_18.
  9. 9. The method according to claim 7 or 8, wherein said pattern of expression levels is determined of at least four, preferably at least five and more preferably at least ten predetermined RNAs of said group.
  10. 10. The method according to one of claims 1 to 9, wherein said expression level or said pattern of expression levels is determined of at least one predetermined RNA or at least three predetermined RNAs selected from the group consisting of Pou2af1 , 2010016l18Rik, A430072P03Rik, Arhgef16, Gm12374, Gm43581 , Gm5431 , 9330160F10Rik, PlatrlO, Gm21986, Gm26632, 5031415H12Rik, Mrpl45, Reps2, Sncaip, Tug1 , Gm43062, Scrn1 , AC165261.1 , Eif4g3, Gm7331.
  11. 11 . The method according to one of claims 1 to 10, wherein said expression level or said pattern of expression levels is determined of at least one predetermined RNA or at least three predetermined RNAs selected from the group consisting of Pou2af1 (ST), 2010016118Rik (ST), A430072P03Rik (ST), Arhgef16 (AS), Gm12374 (ST), Gm43581 (ST), Gm5431 (AS), 9330160F10Rik (ST), PlatrlO (ST), Gm21986 (ST), Gm26632 (ST), 5031415H12Rik (ST), Mrpl45 (ST), Reps2 (AS), Sncaip (ST), Tug1 (ST), Gm43062 (ST), Scrnl (AS), AC165261.1 (ST), Eif4g3 (AS), Gm7331 (ST); or wherein said expression level or said pattern of expression levels is determined of at least one predetermined RNA or at least three predetermined RNAs selected from the group consisting of SEQ_NO_1 to SEQ_NO_21 .
  12. 12. The method according to claim 10 or 11 , wherein said pattern of expression levels is determined of at least four, preferably at least five and more preferably at least ten predetermined RNAs of said group.
  13. 13. The method according to one of claims 1 to 12, wherein said expression level or said pattern of expression levels is determined of the at least one predetermined RNA, preferably least two predetermined RNAs which are upregulated.
  14. 14. The method according to one of claims 1 to 13, wherein said comparison of said determined expression level to said one or several reference expression levels or said comparison of said pattern of expression levels to said one or several reference pattern of expression levels is achieved by determining the presence of at least one predetermined RNA or of at least two predetermined RNAs selected from the group consisting of Pou2af1 , 2010016118Rik, A430072P03Rik, Arhgef16, Gm 12374, Gm43581 , Gm5431 , 9330160F10Rik, PlatrlO, Gm21986, Gm26632, 5031415H12Rik, Mrpl45, Reps2, Sncaip, Tug1 , Gm43062, Scrnl , AC165261.1 , Eif4g3, Gm7331.
  15. 15. The method according to one of claims 1 to 14, wherein said comparison of said determined expression level to said one or several reference expression levels or said comparison of said pattern of expression levels to said one or several reference pattern of expression levels is achieved by determining the presence of at least one predetermined RNA or of at least two predetermined RNAs selected from the group consisting of Pou2af1 (ST), 2010016118Rik (ST), A430072P03Rik (ST), Arhgef16 (AS), Gm 12374 (ST), Gm43581 (ST), Gm5431 (AS), 9330160F10Rik (ST), PlatrlO (ST), Gm21986 (ST), Gm26632 (ST), 5031415H12Rik (ST), Mrpl45 (ST), Reps2 (AS), Sncaip (ST), Tug1 (ST), Gm43062 (ST), Scrnl (AS), AC165261.1 (ST), Eif4g3 (AS), Gm7331 (ST); or wherein said comparison of said determined expression level to said one or several reference expression levels or said comparison of said pattern of expression levels to said one or several reference pattern of expression levels is achieved by determining the presence of at least one predetermined RNA or of at least two predetermined RNAs selected from the group consisting of SEQ_NO_1 to SEQ_NO_21.
  16. 16. The method according to claim 15 or 16, wherein said determined expression level or said pattern of expression levels is achieved without a normalization step.
  17. 17. The method according to one of claims 1 to 16, wherein said at least one biological fluid is selected from the group consisting of blood, blood plasma, serum, lymph, cerebrospinal fluid, tear fluid, urine, and saliva.
  18. 18. The method according to one of claims 1 to 17, wherein said at least one biological fluid is processed to achieve a cell-free sample prior to step a) or said at least one biological fluid is a cell-free sample.
  19. 19. The method according to one of claims 1 to 18, wherein said at least one biological fluid is processed to achieve a vesicle-free sample prior to step a) or said at least one biological fluid is a vesicle-free sample.
  20. 20. The method according to one of claims 1 to 19, wherein said at least one biological fluid is processed to achieve a plasma sample prior to step a).

Description

A method for an in vitro diagnosis, prognosis, staging and/or treatment monitoring of a neurodegenerative disease, neurological disease or amyloid p- related disease The present invention relates to a method for an in vitro diagnosis, prognosis, staging and/or treatment monitoring of a neurodegenerative disease, neurological disease or amyloid [3-related disease. Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by progressive loss of cognitive function and pathologically by extracellular deposition of amyloid-beta peptide (AR>) and intracellular deposition of hyper-phosphorylated tau protein in neurofibrillary tangles in the brain, associated with progressive neuronal degeneration (Marcus et al. J Neurogenet. 2011 ; 25(4): 127-33; Gotz et al, Br J Pharmacol. 2012; 165(5): 1246-59). AD is the most common form of dementia. Approximately 46.8 million people worldwide currently live with AD or other types of dementia. With an ageing population, this number is estimated to increase to 131.5 million by 2050 (World Alzheimer Report, 2015). As such, AD is becoming an increasingly important burden on the affected individuals and their families as well as economic and social costs on medical and healthcare resources in both developed and emerging countries. Dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD), both called Lewy body dementias, are the second most common type of degenerative dementia in patients older than 65 years and their brain pathological hallmarks are alpha-synuclein neuronal inclusions (Lewy bodies, and Lewy neurites), accompanied by neuronal loss (Lancet. 2015 Oct 24; 386(10004): 1683-97). Variants in three genes APOE, SNCA, and GBA have been associated with an increased risk of dementia with Lewy bodies, but in most cases, the cause is unknown. Frontotemporal dementia (FTD) is the third most common dementia across all age groups and the 1st or the 2nd (after AD) prevalent dementia in the 45-64 years age group. The most common form is known as behavioral variant frontotemporal dementia (bvFTD), which is characterized (in its early stages) by changes in personality, behavior, and judgment. Other disorders under the “frontotemporal disorders” umbrella include Pick’s disease, primary progressive aphasia, primary non-fluent aphasia, semantic dementia, corticobasal degeneration (CBD) syndrome, progressive supranuclear palsy (PSP), frontotemporal dementia (FTD) with parkinsonism, and FTD with amyotrophic lateral sclerosis (ALS). Further amyloid [3-related diseases are e.g. amyloidosis. Abnormal protein accumulation is a feature observed in the following diseases: amyloidosis, Alzheimer’s disease, Parkinson’s disease, Creutzfeldt-Jakob disease, motor neuron diseases and the large group of polyglutamine disorders, including Huntington’s disease (Merlini, Giampaolo; Bellotti, Vittorio (2003). Molecular Mechanisms of Amyloidosis. New England Journal of Medicine, 349(6), 583-596. doi:10.1056/nejmra023144; Koo EH, Lansbury PT Jr, Kelly JW. Amyloid diseases: abnormal protein aggregation in neurodegeneration. Proc Natl Acad Sci U S A. 1999 Aug 31 ;96(18):9989-90. doi: 10.1073/pnas.96.18.9989). Based on these issues, various RNAs have been proposed as biomarkers for the detection of Alzheimer's disease, for example, as described in the documents EP 2733219 A1 , EP 3184646 A1 , EP 3725882 A1 , WO 2015/091902 A2, WO 2019/048500 A1 and WO 2020/049135 A1 . Overall, the existing tests either lack an easy accessibility and simplicity for use for diagnosis of the large AD population and/or lack accuracy (sensitivity and specificity). This represents a major impediment and bottleneck to develop reliable and rapid diagnosis tests for AD. Another impediment is the identification of a biomarker that does not require invasive sample collecting, such as a spinal tap. The lack of such an accessible, sensitive and specific biomarker, that could be validated by cellular, animal model, pre-clinical models, and human testing, impedes the development of therapies and drugs for AD or the study of pathological processes triggering AD or involved in the progression of AD. Today, clearly there is a high unmet medical need for efficient preventive or disease-modifying therapeutic treatment, as well as for an accurate and non-invasive peripheral biomarker test for early diagnosis of AD including preclinical and early MCI and for applications in drug development (patient stratification and repeated monitoring of drug efficacy in clinical trials), to monitor the efficacy and to adjust the dosing of potential future therapies.. Likewise, for non-AD dementia, including DLB and for many FTD related neurodegenerative disorders, there is a high unmet medical need for efficient preventive or disease-modifying therapeutic treatment, and for an accurate and non- invasive peripheral biomarker test for diagnosis in particular of their early forms. Thus, even in view of the results achieved withi