Methods of using small rna from bodily fluids for diagnosis and monitoring of neurodegenerative diseases

Abstract

Described are methods for detection of neuronal pathologies using quantitative analysis in bodily fluids of synapse and/or neurite small RNAs and application of these methods to early diagnosis and monitoring of neurodegenerative diseases and other neurological disorders.

1 - 6 . (canceled) 
     
     
         7 . A method for diagnosing Alzheimer's disease (AD) in a subject, which comprises:
 a. determining the level of at least one synapse or neurite small RNA in a bodily fluid sample from the subject;   b. comparing the level of the small RNA in the bodily fluid sample from the subject with a control level of the small RNA, and   c. (i) identifying the subject as being afflicted with AD when the level of the small RNA in the bodily fluid sample from the subject is increased as compared to the control or (ii) identifying the subject as not being afflicted with AD when the level of the small RNA in the bodily fluid sample from the subject is not increased as compared to the control.   
     
     
         8 . The method of  claim 7 , wherein AD is diagnosed prior to massive neuronal cell death characteristic of AD. 
     
     
         9 - 13 . (canceled) 
     
     
         14 . The method of  claim 7 , wherein the small RNA is miRNA. 
     
     
         15 . The method of  claim 14 , wherein the miRNA is a member selected from the group consisting of miR-7, miR-9, miR-9*, miR-25, miR-26a, miR-26b, miR-98, miR-124, miR-125b, miR-128, miR-132, miR-134, miR-138, miR-146, miR-182, miR-183, miR-200b, miR-200c, miR-213, miR-292-5p, miR-297, miR-322, miR-323-3p, miR-325, miR-337, miR-339, miR-345, miR-350, miR-351, miR-370, miR-425, miR-429, miR-433-5p, miR-446, miR-467, and miR-874. 
     
     
         16 . (canceled) 
     
     
         17 . The method of  claim 7 , wherein the control level of the small RNA is the level of said small RNA in a similarly processed bodily fluid sample from an age-matched control subject. 
     
     
         18 . The method of  claim 7 , wherein the control level of the small RNA is the level of said small RNA in a similarly processed bodily fluid sample from the same subject obtained in the past. 
     
     
         19 . The method of  claim 7 , wherein the control level of the small RNA is a predetermined standard. 
     
     
         20 - 23 . (canceled) 
     
     
         24 . The method of  claim 7 , wherein the bodily fluid sample is blood plasma. 
     
     
         25 . (canceled) 
     
     
         26 . The method of  claim 7 , wherein, prior to step (a), the small RNA is purified from the bodily fluid sample. 
     
     
         27 - 30 . (canceled) 
     
     
         31 . A method for monitoring the effectiveness of a treatment of a neuronal pathology in a subject, which comprises:
 a. determining the level of at least one synapse or neurite small RNA in a bodily fluid sample from the subject obtained prior to initiation of the treatment;   b. determining the level of the small RNA in one or more bodily fluid sample(s) from the subject obtained in the course of or following the treatment, and   c. comparing the level of the small RNA determined in steps (a) and (b), and optionally between different samples in step (b).   
     
     
         32 . The method of  claim 31 , which further comprises (d) (i) determining that the treatment is effective if the level of the small RNA has decreased in the course of or following the treatment or (ii) determining that the treatment is not effective if the level of the small RNA has not decreased in the course of or following the treatment. 
     
     
         33 - 37 . (canceled) 
     
     
         38 . The method of  claim 31 , wherein the small RNA is miRNA. 
     
     
         39 . The method of  claim 38 , wherein the miRNA is a member selected from the group consisting of miR-7, miR-9, miR-9*, miR-25, miR-26a, miR-26b, miR-98, miR-124, miR-125b, miR-128, miR-132, miR-134, miR-138, miR-146, miR-182, miR-183, miR-200b, miR-200c, miR-213, miR-292-5p, miR-297, miR-322, miR-323-3p, miR-325, miR-337, miR-339, miR-345, miR-350, miR-351, miR-370, miR-425, miR-429, miR-433-5p, miR-446, miR-467, and miR-874. 
     
     
         40 - 48 . (canceled) 
     
     
         49 . A tool for detecting neurite destruction and synapse loss, associated with a neuronal pathology, or for monitoring a neuronal pathology or for monitoring the effectiveness of a treatment of a neuronal pathology comprising primers and/or probes for one or more miRNA selected from the group consisting of miR-7, miR-9, miR-9*, miR-25, miR-26a, miR-26b, miR-98, miR-124, miR-125b, miR-128, miR-132, miR-134, miR-138, miR-146, miR-182, miR-183, miR-200b, miR-200c, miR-213, miR-292-5p, miR-297, miR-322, miR-323-3p, miR-325, miR-337, miR-339, miR-345, miR-350, miR-351, miR-370, miR-425, miR-429, miR-433-5p, miR-446, miR-467, and miR-874, and further comprising primers and/or probes for one or more miRNA selected from the group consisting of miR-181a, miR-491-5p, miR-10b, and miR-141.