Granted Patent B2

US 12,569,483 · App. 17/613,000 · Granted Mar 10, 2026

Inventor: Alexander Bogdan Niculescu (Indianapolis, IN)

Assignees: Indiana University Research and Technology Corporation; The United States Government as Represented by the Department of Veterans Affairs

A61K31/496A61K31/202A61K33/00A61K45/06G16B25/10

Abstract

Claims (10)

1 . A method for assessing a low memory state in a subject, the method comprising:

a) obtaining RNA expression level data for a panel of biomarkers from a biological sample of a subject, wherein the panel of biomarkers comprises RAB7A, Niemann-Pick disease, type C (NPC2), transforming growth factor beta 1 (TGFB1), growth associated protein 43 (GAP43), arylsulfatase B (ARSB), period circadian clock 1 (PER1), glucuronidase, beta (GUSB), microtubule associated protein tau (MAPT), Fc fragment of IgG, high affinity Ia, receptor (CD64) (FCGR1A), ubiquitin conjugating enzyme E2L 3 (UBE2L3), natural killer cell triggering receptor (NKTR), Ras homolog enriched in brain (RHEB), prostaglandin-endoperoxide synthase 2 (PTGS2), regulator of G-protein signaling 10 (RGS10), inositol-trisphosphate 3-kinase B (ITPKB), kinase D-interacting substrate 220 kDa (KIDINS220), glycogen synthase kinase 3 beta (GSK3B), SERTA domain containing 3 (SERTAD3), apolipoprotein E (APOE), ubiquitin conjugating enzyme E2I (UBE2I), forkhead box O3 (FOXO3), thyroid hormone receptor, alpha (THRA), insulin-like growth factor 1 (IGF1), neuronal pentraxin II (NPTX2), glutathione S-transferase mu 3 (GSTM3), Beta-Secretase 1 (BACE1), presenilin 1 (PSEN1), glial fibrillary nacidic protein (GFAP), triggering receptor expressed on myeloid cells 2 (TREM2), nocturnin (NOCT), centrosomal protein 350 kDa (CEP350), protein phosphatase 2, regulatory subunit B (PPP2R2B), neuropilin 2 (NRP2), cathepsin S (CTSS), and vascular endothelial growth factor A (VEGFA);

b) computing a score based on RNA level, protein level, DNA methylation, or a single nucleotide polymorphism, for the panel of biomarkers in the sample obtained from the subject;

c) computing a reference score based on a reference expression levels for the biomarkers of the panel of biomarkers; and

d) identifying in the sample obtained from the subject as compared to the reference score an increase in expression of RAB7A, TGFB1, GAP43, ARSB, PER1, MAPT, FCGR1A, RGS10, KIDINS220, FOXO3, THRA, IGF1, NPTX2, BACE1, GFAP, TREM2, PPP2R2B, NRP2 and VEGFA in the sample obtained from the subject and a decrease in expression of NPC2, GUSB, UBE2L3, NKTR, RHEB, PTGS2, GSK3B, SERTAD3, APOE, UBE2I, GSTM3, PSEN1, NOCT, CEP350, and CTSS in the sample obtained from the subject, wherein such changes in expression indicates a low memory state in the subject;

e) wherein upon identifying a risk of low memory state in the subject, administering a treatment to the subject wherein the treatment reduces the difference between the score of the sample from the subject and the reference score and wherein a change in score upon administering the treatment indicates a response to the treatment; and

wherein the treatment is a therapy selected from the group consisting of antidepressants, lithium, omega-3 fatty acids, pioglitazone, levonorgestrel, mesalazine, salsolidine, ginkgolide A, icariin, or a combination thereof.

2 . The method of claim 1 , further comprising measuring response to treatment by repeating the steps of the method of claim 1 .

3 . The method of claim 1 wherein the indication of a low memory state in the subject is an indication of risk of future Alzheimer Disease.

4 . The method of claim 1 , wherein the therapy is mesalazine.

Assignments (2)

Continuity (2)

References Cited (27)