JP-2022536523-A5 -

Dates

Publication Date

20230518

Application Date

20200611

Description

In yet another embodiment, the drug therapy is a cholinesterase inhibitor or an N-methyl D-aspartate receptor agonist. In embodiments of the present invention, for example, the following items are provided. (Item 1) A method for determining the risk of Alzheimer's disease in an individual, wherein the method is A step of obtaining a biological sample of an individual or a step of having said sample, wherein the biological sample comprises a dicarboxylic acid; A step of adding an internal standard of dicarboxylic acid molecules to the biological sample; A step of performing an assay on the biological sample to determine the amount of at least one long-chain dicarboxylic acid species in the sample, wherein the determined amount of the at least one long-chain dicarboxylic acid species indicates the risk of Alzheimer's disease in the individual. A method of including. (Item 2) The method according to item 1, wherein the biological sample is urine. (Item 3) The assay is gas chromatography combined with mass spectrometry, according to the method of item 1 or 2. (Item 4) The method according to item 3, further comprising the step of converting the dicarboxylic acid in the biological sample to a dipentafluorobenzyl ester before performing gas chromatography in combination with mass spectrometry. (Item 5) The method according to any one of items 1 to 4, wherein the internal standard of the dicarboxylic acid molecule includes at least one of succinic acid (C4), glutaric acid (C5), pimelic acid (C7), suberic acid (C8), azelaic acid (C9), and sebacic acid (C10). (Item 6) The method according to any one of items 1 to 5, wherein the internal standard of the dicarboxylic acid molecules is a set of deuterated dicarboxylic acid molecules having known concentrations. (Item 7) The method according to any one of items 1 to 6, wherein the amount of at least one long-chain dicarboxylic acid species is a relative amount to the set of one or more dicarboxylic acid species being measured. (Item 8) The method according to any one of items 1 to 6, wherein the amount of at least one long-chain dicarboxylic acid species is the concentration. (Item 9) The method according to any one of items 1 to 8, wherein the determined amount of the at least one long-chain dicarboxylic acid species in the individual is greater than a threshold, and the individual is determined to be at high risk of Alzheimer's disease based on the amount of the at least one long-chain dicarboxylic acid species being greater than the threshold. (Item 10) The method according to item 9, wherein the threshold is based on the amount of at least one long-chain dicarboxylic acid species in a cognitively healthy population or a population of individuals with Alzheimer's disease. (Item 11) The method according to any one of items 1 to 10, wherein the at least one long-chain dicarboxylic acid species is pimelic acid (C7), suberic acid (C8), azelaic acid (C9), sebacic acid (C10), an unsaturated C7, C8, C9 or C10 dicarboxylic acid species, or a substituted C7, C8, C9 or C10 dicarboxylic acid species. (Item 12) A step of performing an assay on the biological sample to determine the relative amount of at least one short-chain dicarboxylic acid species in the sample; and A step of determining the ratio of the relative amount of at least one long-chain dicarboxylic acid species to the relative amount of at least one short-chain dicarboxylic acid species, wherein the determined ratio indicates the risk of Alzheimer's disease in the individual. The method described in any one of items 1 to 11, which further encompasses the method described in item 1 to 11. (Item 13) The method according to item 12, wherein the ratio determined by the individual is greater than a threshold, and the individual is determined to have a high risk of Alzheimer's disease based on the fact that the ratio is greater than the threshold. (Item 14) The method according to item 13, wherein the threshold is based on the ratio of the concentration of at least one long-chain dicarboxylic acid species to the concentration of at least one short-chain dicarboxylic acid species in a cognitively healthy population or a population of individuals with Alzheimer's disease. (Item 15) The method according to item 12, 13, or 14, wherein the at least one short-chain dicarboxylic acid species is succinic acid (C4), glutaric acid (C5), an unsaturated C4 or C5 dicarboxylic acid species, or a substituted C4 or C5 dicarboxylic acid species. (Item 16) A step of obtaining at least a second biological sample of the organism or a step of having such sample, wherein each of the obtained biological samples contains a dicarboxylic acid, and at least two of the biological samples were obtained at two different time points in time; The process of adding an internal standard of dicarboxylic acid molecules to each biological sample; and A step of performing an assay on each of the aforementioned biological samples to determine the concentratio