Multiplex biomarker for use in evaluation of state of accumulation of amyloid B in brain, and analysis method for said evaluation
View Patent ↗Provided are a biomarker for evaluating a cerebral Aβ accumulation state using amyloid precursor protein (APP)-derived Aβ and Aβ-like peptides in a living body-derived sample as an index, and a method for analysis thereof. A marker for determining a cerebral Aβ accumulation state, the marker comprising a combination of at least two ratios selected from the group consisting of: a ratio of Aβ1-39 (SEQ ID NO.: 1) level to Aβ1-42 (SEQ ID NO.: 3) level: Aβ1-39/Aβ1-42; a ratio of Aβ1-40 (SEQ ID NO.: 2) level to Aβ1-42 (SEQ ID NO.: 3) level: Aβ1-40/Aβ1-42; and a ratio of APP669-711 (SEQ ID NO.: 4) level to Aβ1-42 (SEQ ID NO.: 3) level: APP669-711/Aβ1-42, in a living body-derived sample.
1. A method for treating an Alzheimer patient, comprising
(a) determining a cerebral Aβ accumulation state in a subject to determine presence or stage of Alzheimer disease in the subject, comprising:
detecting, in a living body-derived sample from the subject:
Aβ1-42 (SEQ ID NO.: 3);
Aβ1-39 (SEQ ID NO.: 1); and
at least one selected from the group consisting of Aβ1-40 (SEQ ID NO.: 2), and APP669-711 (SEQ ID NO.: 4), and
obtaining (i) a ratio of Aβ1-39 level to Aβ1-42 level (Aβ1-39/Aβ1-42); and (ii) at least one ratio selected from the group consisting of: a ratio of Aβ1-40 level to Aβ1-42 level (Aβ1-40/Aβ1-42); and a ratio of APP669-711 level to Aβ1-42 level (APP669-711/Aβ1-42); and
(b) treating the subject by administering a therapeutic drug for Alzheimer, wherein the subject has a higher Aβ1-39/Aβ1-42; and (ii) a higher Aβ1-40/Aβ1-42 or APP669-711/Aβ1-42 compared to a control subject.
2. The method according to claim 1 , wherein the living body-derived sample is selected from the group consisting of blood, cerebrospinal fluid, urine, and feces.
3. The method according to claim 1 , wherein the living body-derived sample is blood.
4. The method according to claim 1 , wherein the determining a cerebral Aβ accumulation state comprises detecting said Aβ1-40 (SEQ ID NO.: 2).
5. The method according to claim 1 , wherein the determining a cerebral Aβ accumulation state comprises detecting said APP669-711 (SEQ ID NO.: 4).
6. The method according to claim 1 , wherein the determining a cerebral Aβ accumulation state comprises detecting said Aβ1-40 (SEQ ID NO.: 2) and said APP669-711 (SEQ ID NO.: 4).
7. The method according to claim 1 , wherein the determining a cerebral Aβ accumulation state comprises obtaining said Aβ1-40/Aβ1-42.
8. The method according to claim 1 , wherein the determining a cerebral Aβ accumulation state comprises obtaining said APP669-711/Aβ1-42.
9. The method according to claim 1 , wherein the determining a cerebral Aβ accumulation state comprises obtaining said Aβ1-40/Aβ1-42 and said APP669-711/Aβ1-42.
10. The method according to claim 1 , wherein step (a) determines the presence of the Alzheimer disease.
11. The method according to claim 1 , wherein step (a) determines the stage of the Alzheimer disease.
12. The method according to claim 1 , wherein the living body-derived sample is plasma.
13. The method according to claim 1 , wherein the detecting is performed by a mass spectrometer.
14. The method according to claim 1 , wherein the living body-derived sample is blood;
the determining a cerebral Aβ accumulation state comprises detecting said APP669-711 (SEQ ID NO.: 4) and obtaining said APP669-711/Aβ1-42; the detecting is performed by a mass spectrometer; and the subject has the higher APP669-711/Aβ1-42 compared to a control subject.