DK2575596T3 - Fremgangsmåde til bestemmelse af amyloid-beta-omsætning i blod. - Google Patents
Fremgangsmåde til bestemmelse af amyloid-beta-omsætning i blod. Download PDFInfo
- Publication number
- DK2575596T3 DK2575596T3 DK11787251.5T DK11787251T DK2575596T3 DK 2575596 T3 DK2575596 T3 DK 2575596T3 DK 11787251 T DK11787251 T DK 11787251T DK 2575596 T3 DK2575596 T3 DK 2575596T3
- Authority
- DK
- Denmark
- Prior art keywords
- labeled
- hours
- label
- blood
- amino acid
- Prior art date
Links
- 239000008280 blood Substances 0.000 title claims description 80
- 210000004369 blood Anatomy 0.000 title claims description 80
- 238000000034 method Methods 0.000 title claims description 40
- 150000001413 amino acids Chemical class 0.000 claims description 38
- 230000007306 turnover Effects 0.000 claims description 28
- 238000001802 infusion Methods 0.000 claims description 13
- 230000002285 radioactive effect Effects 0.000 claims description 9
- 238000011002 quantification Methods 0.000 claims description 6
- 238000001990 intravenous administration Methods 0.000 claims description 5
- 238000004949 mass spectrometry Methods 0.000 claims description 5
- 238000001727 in vivo Methods 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 238000000338 in vitro Methods 0.000 claims 1
- 235000001014 amino acid Nutrition 0.000 description 29
- 229940024606 amino acid Drugs 0.000 description 29
- 108090000765 processed proteins & peptides Proteins 0.000 description 15
- 239000011324 bead Substances 0.000 description 12
- 230000004060 metabolic process Effects 0.000 description 12
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- 210000003169 central nervous system Anatomy 0.000 description 8
- 102000004196 processed proteins & peptides Human genes 0.000 description 8
- 150000002500 ions Chemical class 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 208000024827 Alzheimer disease Diseases 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 5
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 5
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 5
- 102000001708 Protein Isoforms Human genes 0.000 description 5
- 108010029485 Protein Isoforms Proteins 0.000 description 5
- 102000004142 Trypsin Human genes 0.000 description 5
- 108090000631 Trypsin Proteins 0.000 description 5
- 235000019253 formic acid Nutrition 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 238000002552 multiple reaction monitoring Methods 0.000 description 5
- 210000002381 plasma Anatomy 0.000 description 5
- 239000012588 trypsin Substances 0.000 description 5
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 4
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000003797 essential amino acid Substances 0.000 description 4
- 235000020776 essential amino acid Nutrition 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000002372 labelling Methods 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 238000001114 immunoprecipitation Methods 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 230000032258 transport Effects 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 238000013467 fragmentation Methods 0.000 description 2
- 238000006062 fragmentation reaction Methods 0.000 description 2
- 229960000789 guanidine hydrochloride Drugs 0.000 description 2
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 2
- 238000001948 isotopic labelling Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000007310 pathophysiology Effects 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 230000035479 physiological effects, processes and functions Effects 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- 238000004780 2D liquid chromatography Methods 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 208000037259 Amyloid Plaque Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 241000512259 Ascophyllum nodosum Species 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 241001474374 Blennius Species 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 101710118538 Protease Proteins 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 239000012503 blood component Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 238000011210 chromatographic step Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 235000004554 glutamine Nutrition 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 238000012001 immunoprecipitation mass spectrometry Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 231100000863 loss of memory Toxicity 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000004898 n-terminal fragment Anatomy 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
- G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
- G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
- G01N2333/4701—Details
- G01N2333/4709—Amyloid plaque core protein
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Pathology (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Food Science & Technology (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Microbiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Optics & Photonics (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
Claims (11)
1
1. In vitro-fremgangsmåde til måling af in vivo-omsætningen af Αβ i blodet fra et subjekt, hvor fremgangsmåden omfatter: (a) at bestemme mængden af mærket Αβ ved massespektroskopi eller mængden af såvel mærket Αβ og ikke-mærket Αβ i en blodprøve opnået fra subjektet; og (b) at beregne omsætningen af Αβ ved anvendelse af mængden af mærket Αβ eller mængden af såvel mærket Αβ og ikke-mærket Αβ, bestemt i trin (a), hvor (i) Αβ-omsætning beregnes fra mængden af mærket Αβ eller mængden af mærket Αβ og ikke-nærket Αβ, i en prøve opnået mellem 15 minutter og 4 timer efter oral eller intravenøs indgivelse er påbegyndt, af mindst én aminosyre, der er mærket med en stabil ikke-radioaktiv isotop til subjektet; eller (ii) Αβ-omsætning bestemmes fra maksimumsværdien af fremstillingen af mærket Αβ, der sker mellem omkring 1 og 5 timer efter oral bolusindgivelse påbegyndes af mindst én aminosyre, der er mærket med en stabil ikke-radioaktiv isotop til subjektet eller mellem omkring 5 og 10 timer efter intravenøs indgivelse påbegyndes ved en 9 timers infusion af mindst én aminosyre, der er mærket med en stabil ikke-radioaktiv isotop til subjektet.
2. Fremgangsmåde ifølge krav 1, hvor den orale bolusindgivelse af del (b)(ii) substitueres med en IV-bolus.
3. Fremgangsmåde ifølge krav 1, hvor den mærkede aminosyre indgives oralt.
4. Fremgangsmåde ifølge krav 3, hvor mellem omkring 0,05g og omkring 8g af aminosyre, der er mærket med en stabil ikke-radioaktiv isotop indgives.
5. Fremgangsmåde ifølge krav 1, hvor den mærkede aminosyre indgives intravenøst.
6. Fremgangsmåde ifølge krav 5, hvor den mærkede aminosyre indgives som en infusion ved mellem omkring 0,01mg/kg/hour og omkring 3 mg/kg/hour.
7. Fremgangsmåde ifølge krav 1, hvor trin (a) yderligere omfatter indledningsvist at isolere Αβ fra blodprøven.
8. Fremgangsmåde ifølge krav 1, hvor den mindst éne blodprøve tages efter omkring 30 minutter efter indgivelse af mindst én mærket aminosyre til subjektet.
9. Fremgangsmåde ifølge krav 1, hvor mængden af mærket Αβ eller ikke-mærket Αβ er valgt fra gruppen bestående af samlet Αβ, Αβ38, Αβ40, og Αβ42.
10. Fremgangsmåde ifølge krav 1, yderligere omfattende at bestemme den absolutte kvantificering af Αβ i prøven.
11. Fremgangsmåde ifølge krav 10, hvor omsætningen af Αβ bestemmes ved anvendelse af produktet af den procentvise mærkede Αβ og den absolutte kvantificering af Αβ.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US34755410P | 2010-05-24 | 2010-05-24 | |
| PCT/US2011/037754 WO2011149947A2 (en) | 2010-05-24 | 2011-05-24 | Methods of determining amyloid beta turnover in blood |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2575596T3 true DK2575596T3 (da) | 2016-08-01 |
Family
ID=45004715
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK11787251.5T DK2575596T3 (da) | 2010-05-24 | 2011-05-24 | Fremgangsmåde til bestemmelse af amyloid-beta-omsætning i blod. |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US20130115716A1 (da) |
| EP (2) | EP2575596B1 (da) |
| JP (2) | JP5886837B2 (da) |
| KR (1) | KR20130116792A (da) |
| AU (1) | AU2011258462B2 (da) |
| BR (1) | BR112012029985A2 (da) |
| CA (1) | CA2800680C (da) |
| DK (1) | DK2575596T3 (da) |
| ES (1) | ES2583033T3 (da) |
| WO (1) | WO2011149947A2 (da) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090142766A1 (en) * | 2007-11-09 | 2009-06-04 | Washington University In St. Louis | Methods for measuring the metabolism of cns derived biomolecules in vivo |
| JP6129868B2 (ja) * | 2011-12-19 | 2017-05-17 | ワシントン・ユニバーシティＷａｓｈｉｎｇｔｏｎ Ｕｎｉｖｅｒｓｉｔｙ | アルツハイマー病を診断するための方法 |
| WO2014160647A1 (en) * | 2013-03-24 | 2014-10-02 | The Washington University | Method for amyloid beta sample processing |
| ES2874704T3 (es) * | 2013-11-20 | 2021-11-05 | Univ Iowa Res Found | Procedimiento para monitorizar la eficacia de un tratamiento de la enfermedad de Alzheimer con una isoforma de ApoE |
| BR112017006419A2 (pt) | 2014-09-30 | 2017-12-19 | Univ Washington | medições cinéticas de tau |
| CN108348776A (zh) * | 2015-06-30 | 2018-07-31 | 健康研究公司 | 基于测定蛋白水解通路对阿尔茨海默病进行的诊断检验 |
| WO2018204406A1 (en) | 2017-05-01 | 2018-11-08 | Washington University | BLOOD-BASED METHODS FOR DETERMINING Aβ AMYLOIDOSIS |
| US11085935B2 (en) | 2018-05-03 | 2021-08-10 | Washington University | Methods of treating based on site-specific tau phosphorylation |
| WO2021009074A1 (en) | 2019-07-12 | 2021-01-21 | Adx Neurosciences Nv | Novel markers as early predictors of alzheimer's pathology |
| KR20220062024A (ko) | 2019-09-10 | 2022-05-13 | 워싱턴 유니버시티 | 부위-특이적 tau 포스포릴화를 기반으로 한 진단 및 치료를 위한 혈액-기반 검정 |
| EP4204814A4 (en) * | 2020-08-27 | 2024-10-23 | The Regents of the University of Colorado, a body corporate | Method for determining medication adherence and taggants therefor |
| EP4296660A4 (en) * | 2021-02-22 | 2025-04-23 | Shimadzu Corporation | Calibrant for use in mass spectrometer and method for producing same |
| WO2024133743A1 (en) * | 2022-12-21 | 2024-06-27 | EM Scientific Limited | Method for diagnosing and/or classifying the severity of a neurodegenerative disease |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7449171B2 (en) * | 2002-02-12 | 2008-11-11 | The Regents Of The University Of California | Measurement of biosynthesis and breakdown rates of biological molecules that are inaccessible or not easily accessible to direct sampling, non-invasively, by label incorporation into metabolic derivatives and catabolic products |
| US20040096907A1 (en) * | 2002-11-06 | 2004-05-20 | Bernd Bohrmann | Quantification of beta amyloid |
| US20080187937A1 (en) * | 2004-08-07 | 2008-08-07 | Hellerstein Marc K | Method For Measuring Dynamics Of Self-Assembling Systems Of Biological Molecules In Vivo And Uses For Discovering Or Evaluating Therapeutic Agents |
| EP1886112B1 (en) * | 2005-04-06 | 2014-07-09 | Washington University St. Louis | Methods for measuring the metabolism of neurally derived biomolecules in vivo |
| CA2745839C (en) * | 2008-12-05 | 2017-09-19 | C2N Diagnostics | Methods for measuring concentrations of biomolecules |
-
2011
- 2011-05-24 DK DK11787251.5T patent/DK2575596T3/da active
- 2011-05-24 EP EP11787251.5A patent/EP2575596B1/en active Active
- 2011-05-24 BR BR112012029985A patent/BR112012029985A2/pt not_active IP Right Cessation
- 2011-05-24 CA CA2800680A patent/CA2800680C/en active Active
- 2011-05-24 US US13/699,497 patent/US20130115716A1/en not_active Abandoned
- 2011-05-24 KR KR1020127033176A patent/KR20130116792A/ko not_active Ceased
- 2011-05-24 ES ES11787251.5T patent/ES2583033T3/es active Active
- 2011-05-24 JP JP2013512165A patent/JP5886837B2/ja active Active
- 2011-05-24 EP EP16158001.4A patent/EP3066979B1/en active Active
- 2011-05-24 WO PCT/US2011/037754 patent/WO2011149947A2/en not_active Ceased
- 2011-05-24 AU AU2011258462A patent/AU2011258462B2/en active Active
-
2016
- 2016-02-10 JP JP2016023884A patent/JP6293802B2/ja active Active
-
2017
- 2017-02-01 US US15/422,165 patent/US20170146557A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| BR112012029985A2 (pt) | 2017-02-21 |
| EP2575596B1 (en) | 2016-04-20 |
| JP2016153788A (ja) | 2016-08-25 |
| AU2011258462A1 (en) | 2012-12-13 |
| EP2575596A2 (en) | 2013-04-10 |
| ES2583033T3 (es) | 2016-09-16 |
| CA2800680C (en) | 2018-08-28 |
| EP2575596A4 (en) | 2013-12-04 |
| KR20130116792A (ko) | 2013-10-24 |
| WO2011149947A3 (en) | 2012-01-26 |
| JP6293802B2 (ja) | 2018-03-14 |
| EP3066979A1 (en) | 2016-09-14 |
| US20170146557A1 (en) | 2017-05-25 |
| US20130115716A1 (en) | 2013-05-09 |
| CA2800680A1 (en) | 2011-12-01 |
| WO2011149947A2 (en) | 2011-12-01 |
| JP2013532277A (ja) | 2013-08-15 |
| EP3066979B1 (en) | 2017-11-01 |
| AU2011258462B2 (en) | 2015-01-15 |
| JP5886837B2 (ja) | 2016-03-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2575596B1 (en) | Methods of determining amyloid beta turnover in blood | |
| AU2012359020B2 (en) | Methods for diagnosing Alzheimer's disease | |
| Yoshida et al. | Validation of an analytical method for human plasma free amino acids by high-performance liquid chromatography ionization mass spectrometry using automated precolumn derivatization | |
| US11698378B2 (en) | Methods and compositions for tauopathy diagnosis and treatment | |
| EP3200832B1 (en) | Tau kinetic measurements | |
| WO2015014903A2 (en) | Diagnostic tools for alzheimer's disease | |
| Robinson et al. | Release of skeletal muscle peptide fragments identifies individual proteins degraded during insulin deprivation in type 1 diabetic humans and mice | |
| Janzen et al. | UPLC–MS/MS analysis of C5-acylcarnitines in dried blood spots | |
| AU2017200029B2 (en) | Methods of determining amyloid beta turnover in blood | |
| JP2013542453A (ja) | 疾患のバイオマーカーとしてのアルブミン結合タンパク質／ペプチド複合体 | |
| Vanderboom | Plasma Extracellular Vesicles, Exercise Resistance and Cancer | |
| AU2014265047A1 (en) | Simultaneous measurement of the in vivo metabolism of isoforms of a biomolecule | |
| Nair | Release of skeletal muscle peptide fragments identifies individual proteins 1 degraded during insulin deprivation in Type-I Diabetic humans and mice 2 3 Matthew M. Robinson1, Surendra Dasari2, Helen Karakelides1, H. Robert Bergen 3rd 3, 4 and K. Sreekumaran Nair1 5 | |
| Khambule | Association of Branched Chain Amino Acids and Aromatic Amino Acids with Cardiometabolic Risk Factors |