METHODS AND COMPOSITIONS FOR DIAGNOSIS OF ALZHEIMER'S DISEASE
The invention provides a method of diagnosing Alzheimer's disease (AD) in a subject by determining the level of expression of one or more miRNAs molecules associated with AD, as well as various nucleic acid molecules relating thereto or derived thereof.
1 . A method of diagnosing Alzheimer's disease (AD) in a subject, the method comprising: obtaining a biological sample from a subject; determining an expression profile in said sample of a nucleic acid sequence selected from the group consisting of SEQ ID NOS: 1-67; a fragment thereof or a sequence having at least about 80% identity thereto; and comparing said expression profile to a reference expression profile wherein a difference in the level of expression profile in at least one or more nucleic acid sequence in said biological sample compared to said reference expression profile is diagnostic for AD.
2 . The method of claim 1 , wherein relatively high expression levels of a nucleic acid sequence selected from the group consisting of SEQ ID NOS: 1-51; a fragment thereof and a sequence having at least about 80% identity thereto is diagnostic for AD.
3 . The method of claim 1 , wherein relatively low expression levels of a nucleic acid sequence selected from the group consisting of SEQ ID NOS: 52-67; a fragment thereof and a sequence having at least about 80% identity thereto is diagnostic for AD.
4 . The method of claim 1 , wherein said biological sample is selected from the group consisting of bodily fluid, a cell line and a tissue sample.
5 . The method of claim 4 , wherein said bodily fluid sample is a serum sample.
6 . The method of claim 4 , wherein said bodily fluid sample is a blood sample.
7 . The method of claim 1 , wherein the method comprises determining the expression levels of at least two nucleic acid sequences.
8 . The method of claim 7 , wherein the method further comprises combining one or more expression ratios of said nucleic acid sequences.
9 . The method of claim 1 , wherein the expression levels are determined by a method selected from the group consisting of nucleic acid hybridization, nucleic acid amplification, and a combination thereof.
10 . The method of claim 9 , wherein the nucleic acid amplification method is real-time PCR.
11 . The method of claim 10 , wherein the real-time PCR method comprises forward and reverse primers.
12 . The method of claim 11 , wherein the forward primer comprises a sequence selected from the group consisting of SEQ ID NOS: 68-134; a fragment thereof and a sequence having at least about 80% identity thereto.
13 . The method of claim 12 , wherein the real-time PCR method further comprises a probe.
14 . The method of claim 13 , wherein the probe comprises a nucleic acid sequence that is complementary to a sequence selected from the group consisting of SEQ ID NOS: 1-67; a fragment thereof and a sequence having at least about 80% identity thereto.
15 . The method of claim 14 , wherein the probe comprises a nucleic acid sequence selected from the group consisting of SEQ ID NOS: 135-201; a fragment thereof and a sequence having at least about 80% identity thereto.
16 . The method of claim 11 , wherein the reverse primer comprises SEQ ID NO: 202, a fragment thereof and a sequence having at least about 80% identity thereto.
17 . A kit for assessing AD in a subject, said kit comprising a probe comprising a nucleic acid sequence that is complementary to a sequence selected from the group consisting of SEQ ID NOS: 1-67; a fragment thereof and a sequence having at least about 80% identity thereto.
18 . The kit of claim 17 , wherein the probe comprises a nucleic acid sequence selected from the group consisting of SEQ ID NOS: 135-201; a fragment thereof and a sequence having at least about 80% identity thereto.
19 . The kit of claim 17 , wherein the kit further comprises a forward primer comprising a sequence selected from the group consisting of any one of SEQ ID NOS: 68-134; a fragment thereof and a sequence having at least about 80% identity thereto.
20 . The kit of claim 17 , wherein the kit further comprises a reverse primer comprises SEQ ID NO: 202, a fragment thereof and a sequence having at least about 80% identity thereto.
21 . The method of claim 1 , further comprising managing subject treatment based on the AD status.
22 . The method of claim 21 , wherein managing subject treatment is selected from ordering further diagnostic tests and administering at least one therapeutic agent.