Back to results
US 2009/0211346 A1Published application
Methods for Detecting Alzheimer's Disease
AssigneeBG Medicine, Inc.
InventorsDoris Damian, Amir Handzel, Aram Adourian
Life of this patent
Estimating the term…
Abstract
Markers are provided that are predictive of Alzheimer's disease. Levels of these markers, when different from a standard, are indicative of a patient being at risk of having or developing Alzheimer's disease.
Claims61
A method for screening an individual for being at risk of having or developing Alzheimer's disease, the method comprising the step of:
- comparing an amount of each of at least two markers in a sample from a patient with an amount of each of the at least two markers from a standard, wherein a difference in the amount of each of the at least two markers between the sample and the standard indicates a positive screen and wherein the at least two markers are selected from a group of molecules, each molecule of the group characterized by a liquid chromatography retention time and mass-to-charge ratio pair as set forth below:
- Liquid Chromatography
- Retention Time (minutes)
- Mass-to-charge Ratio
- 3.42
- 169
- 10.45
- 246
- 17.14
- 120
- 22.05
- 202
- 10.66
- 254
- 17.98
- 273
- 19.44
- 260
- 8.39
- 153
- 16.07
- 203
- 16.12
- 245
- 10.20
- 218
- 19.29
- 304
- 10.50
- 227
- 16.33
- 333
- 3.48
- 336
- 11.24
- 229
- 17.09
- 222
- 14.57
- 297
- 9.03
- 176
- 11.31
- 274
- 19.41
- 261
- 8.47
- 153
- 15.96
- 220
- 16.05
- 231
- 17.66
- 288
- 23.10
- 304
- 11.27
- 141
- 12.23
- 277
- 14.59
- 278
- 13.13
- 247
- 15.75
- 188
- 19.84
- 304
- 12.59
- 130
- 11.35
- 273
- 19.48
- 186
- 18.24
- 303
- 19.47
- 260
- 10.49
- 254
- 14.20
- 218
- 12.38
- 248
- 11.26
- 197
- 15.09
- 261
- 9.13
- 175
- 10.60
- 185
- 12.71
- 205
- 17.65
- 257
- 15.55
- 265
- 19.34
- 368
- wherein the liquid chromatography retention time is determined by a high performance liquid chromatography system comprising:
- a stationary phase comprising:
- a C18 guard column comprising an inner diameter of 10 mm and a length of 50 mm and including octadecyl-bonded silica particles comprising a mean diameter of about 5 μm, and
- a reverse-phase C18 chromatography column comprising an inner diameter of 3 mm and a length of 100 mm and including octadecyl-bonded silica particles comprising a mean diameter of about 5 μm, and
- a mobile phase comprising:
- a solvent A varying from 0% to 100% by volume of the mobile phase, solvent A comprising a 0.1% aqueous formic acid solution, and
- a solvent B varying from 0% to 100% by volume of the mobile phase, solvent B comprising 80% by volume acetonitrile and 20% by volume of a 0.1% aqueous formic acid solution,
- wherein the mobile phase passes through the stationary phase at ambient temperature and at a rate of 0.3 milliliters per minute and wherein the ratio of solvent A to solvent B decreases linearly from 100:0 to 95:5 over 2.50 minutes, whereupon the ratio of solvent A to solvent B decreases linearly from 95:5 to 60:40 over the next 17.5 minutes, whereupon the ratio of solvent A to solvent B decreases linearly from 60:40 to 0:100 over the next 2.00 minutes, whereupon the ratio of solvent A to solvent B is maintained at 0:100 over the next 8.00 minutes and wherein
- the mass-to-charge ratio is determined by a mass spectrometry system comprising an electrospray ion source and a quadruple ion trap detector scanning in the positive ion mode.
106 more elements
A method for screening an individual for being at risk of having or developing Alzheimer's disease, the method comprising the step of:
- comparing an amount of each of at least two markers in a sample from a patient with an amount of each of the at least two markers from a standard, wherein a difference in the amount of each of the at least two markers between the sample and the standard indicates a positive screen and wherein the markers are selected from the group consisting of:
- phenylalanine, glutamate, carnitine, urate, L-homocitrulline, 4-methylene-glutamate, 4-acetamidobutanoate, 6-amino-2-oxohexanoate, (S)-5-amino-3-oxohexanoate, L-2-aminoadipate-6-semialdehyde, 2-amino-3-oxohexanoate, N4 acetylaminobutanoate, 2-oxohex-trans-4-enoate, nicotinurate, N-acetyl histidine, N-formimino-L-aspartate, cis-aconitate, trans-aconitate, tyrosine ethyl ester, 3-hydroxy-anthranilate, 3-hydroxy-2-methylpyridine-5-carboxylate, 4-amino-salicylate, 1-carbapen-2-em-3-carboxylic acid, saccaropine, 2-(hydroxymethyl)-3-(acetamidomethylene) succinate, and butyl esters thereof.
A method for screening an individual for being at risk of having or developing Alzheimer's disease, the method comprising the step of:
- comparing an amount of each of at least two markers in a sample from a patient with an amount of each of the at least two markers from a standard, wherein a difference in the amount of each of the at least two markers between the sample and the standard indicates a positive screen and wherein a first marker is selected from a group of molecules, each molecule of the group characterized by a liquid chromatography retention time and mass-to-charge ratio pair as set forth below:
- Liquid Chromatography
- Retention Time (minutes)
- Mass-to-charge Ratio
- 3.42
- 169
- 3.48
- 336
- 14.59
- 278
- and a second marker is selected from a group of molecules, each molecule of the group characterized by a liquid chromatography retention time and mass-to-charge ratio pair as set forth below:
- Liquid Chromatography
- Retention Time (minutes)
- Mass-to-charge Ratio
- 10.45
- 246
- 11.24
- 229
- 13.13
- 247
- wherein the liquid chromatography retention time is determined by a high performance liquid chromatography system comprising:
- a stationary phase comprising:
- a C18 guard column comprising an inner diameter of 10 mm and a length of 50 mm and including octadecyl-bonded silica particles comprising a mean diameter of about 5 μm, and
- a reverse-phase C18 chromatography column comprising an inner diameter of 3 mm and a length of 100 mm and including octadecyl-bonded silica particles comprising a mean diameter of about 5 μm, and
- a mobile phase comprising:
- a solvent A varying from 0% to 100% by volume of the mobile phase, solvent A comprising a 0.1% aqueous formic acid solution, and
- a solvent B varying from 0% to 100% by volume of the mobile phase, solvent B comprising 80% by volume acetonitrile and 20% by volume of a 0.1% aqueous formic acid solution,
- wherein the mobile phase passes through the stationary phase at ambient temperature and at a rate of 0.3 milliliters per minute and wherein the ratio of solvent A to solvent B decreases linearly from 100:0 to 95:5 over 2.50 minutes, whereupon the ratio of solvent A to solvent B decreases linearly from 95:5 to 60:40 over the next 17.5 minutes, whereupon the ratio of solvent A to solvent B decreases linearly from 60:40 to 0:100 over the next 2.00 minutes, whereupon the ratio of solvent A to solvent B is maintained at 0:100 over the next 8.00 minutes and wherein
- the mass-to-charge ratio is determined by a mass spectrometry system comprising an electrospray ion source and a quadruple ion trap detector scanning in the positive ion mode.
26 more elements
A method for screening an individual for being at risk of having or developing Alzheimer's disease, the method comprising the step of:
- comparing an amount of each of at least two markers in a sample from a patient with an amount of each of the at least two markers from a standard, wherein a difference in the amount of a statistically significant number of the at least two markers between the sample and the standard indicates a positive screen and wherein the at least two markers are selected from a group of molecules, each molecule of the group characterized by a liquid chromatography retention time and mass-to-charge ratio pair as set forth below:
- Liquid Chromatography
- Retention Time (minutes)
- Mass-to-charge Ratio
- 3.42
- 169
- 10.45
- 246
- 17.14
- 120
- 22.05
- 202
- 10.66
- 254
- 17.98
- 273
- 19.44
- 260
- 8.39
- 153
- 16.07
- 203
- 16.12
- 245
- 10.20
- 218
- 19.29
- 304
- 10.50
- 227
- 16.33
- 333
- 3.48
- 336
- 11.24
- 229
- 17.09
- 222
- 14.57
- 297
- 9.03
- 176
- 11.31
- 274
- 19.41
- 261
- 8.47
- 153
- 15.96
- 220
- 16.05
- 231
- 17.66
- 288
- 23.10
- 304
- 11.27
- 141
- 12.23
- 277
- 14.59
- 278
- 13.13
- 247
- 15.75
- 188
- 19.84
- 304
- 12.59
- 130
- 11.35
- 273
- 19.48
- 186
- 18.24
- 303
- 19.47
- 260
- 10.49
- 254
- 14.20
- 218
- 12.38
- 248
- 11.26
- 197
- 15.09
- 261
- 9.13
- 175
- 10.60
- 185
- 12.71
- 205
- 17.65
- 257
- 15.55
- 265
- 19.34
- 368
- wherein the liquid chromatography retention time is determined by a high performance liquid chromatography system comprising:
- a stationary phase comprising:
- a C18 guard column comprising an inner diameter of 10 mm and a length of 50 mm and including octadecyl-bonded silica particles comprising a mean diameter of about 5 μm, and
- a reverse-phase C18 chromatography column comprising an inner diameter of 3 mm and a length of 100 mm and including octadecyl-bonded silica particles comprising a mean diameter of about 5 μm, and
- a mobile phase comprising:
- a solvent A varying from 0% to 100% by volume of the mobile phase, solvent A comprising a 0.1% aqueous formic acid solution, and
- a solvent B varying from 0% to 100% by volume of the mobile phase, solvent B comprising 80% by volume acetonitrile and 20% by volume of a 0.1% aqueous formic acid solution,
- wherein the mobile phase passes through the stationary phase at ambient temperature and at a rate of 0.3 milliliters per minute and wherein the ratio of solvent A to solvent B decreases linearly from 100:0 to 95:5 over 2.50 minutes, whereupon the ratio of solvent A to solvent B decreases linearly from 95:5 to 60:40 over the next 17.5 minutes, whereupon the ratio of solvent A to solvent B decreases linearly from 60:40 to 0:100 over the next 2.00 minutes, whereupon the ratio of solvent A to solvent B is maintained at 0:100 over the next 8.00 minutes and wherein
- the mass-to-charge ratio is determined by a mass spectrometry system comprising an electrospray ion source and a quadruple ion trap detector scanning in the positive ion mode.
106 more elements
A method for screening an individual for being at risk of having or developing Alzheimer's disease, the method comprising the step of:
- comparing an amount of each of at least two markers in a sample from a patient with an amount of each of the at least two markers from a standard, wherein a difference in the amount of a statistically significant number of the at least two markers between the sample and the standard indicates a positive screen and wherein the markers are selected from the group consisting of:
- phenylalanine, glutamate, carnitine, urate, L-homocitrulline, 4-methylene-glutamate, 4-acetamidobutanoate, 6-amino-2-oxohexanoate, (S)-5-amino-3-oxohexanoate, L-2-aminoadipate-6-semialdehyde, 2-amino-3-oxohexanoate, N4 acetylaminobutanoate, 2-oxohex-trans-4-enoate, nicotinurate, N-acetyl histidine, N-formimino-L-aspartate, cis-aconitate, trans-aconitate, tyrosine ethyl ester, 3-hydroxy-anthranilate, 3-hydroxy-2-methylpyridine-5-carboxylate, 4-amino-salicylate, 1-carbapen-2-em-3-carboxylic acid, saccaropine, 2-(hydroxymethyl)-3-(acetamidomethylene) succinate, and butyl esters thereof.
Dependencies are inferred from the claim text.