TRNA-derived fragments as disease biomarkers and neuropathological regulators in Alzheimer's disease

1 . A method for treating Alzheimer's Disease, the method comprising the steps of:

performing or having performed an assay that determines a level of one or more 5′-tRNA derived RNA fragments (5-tRFs) selected from the group consisting of tRF5-GlyGCC, tRF5-GluCTC, tRF5-GlyCCC-2, tRF5-ProAGG, and tRF5-CysGCA in a hippocampal sample from a human patient suspected of having Alzheimer's Disease when compared to a comparator sample that is a normal, control hippocampal tissue sample;

determining that the hippocampal sample from the human patient has an increase in the tRF5-GlyGCC, tRF5-GluCTC, tRF5-GlyCCC-2, tRF5-ProAGG, and tRF5-CysGCA when compared to the comparator sample; and

administering to the human patient an NSun2 gene when the hippocampal sample from the human patient has an increase in the tRF5-GlyGCC, RF5-GluCTC, tRF5-GlyCCC-2, tRF5-ProAGG, and tRF5-CysGCA.

2 . The method of claim 1 , wherein the level of the one or more 5-tRFs is greater than the level of the 5-tRFs in the comparator sample by at least 1.5, 2.0, 2.5, or 3.0-fold.

3 . The method of claim 1 , wherein the NSun2 gene further comprises a pharmaceutically acceptable carrier, diluent or excipient.

4 . The method of claim 1 , wherein the Alzheimer's Disease is selected from early-onset AD or late-onset AD.

5 . A method of treating Alzheimer's Disease (AD) in a human patient suspected of having AD, the method comprising:

obtaining a cerebrospinal fluid (CSF) sample from the human patient,

determining that the CSF sample from the human patient has an increased level of at least one of: a 5′-tRNA derived RNA fragments (5-tRF) selected from tRF5-GlyCCC-2 and tRF5-ProAGG in the CSF sample,

comparing the level of the one or more 5′-tRNA derived RNA fragments (5-tRF) selected from the group consisting of tRF5-GlyCCC-2 and tRF5-ProAGG in the CSF sample with the level in a comparator sample that is a normal, control CSF sample, wherein the level of 5-tRF in the CSF sample is different than the level in the comparator sample;

determining that the CSF sample from the human patient has an increase in the at least one of tRF5-GlyCCC-2 and tRF5-ProAGG; and

administering to the human patient having an increase in the at least one of tRF5-GlyCCC-2 and tRF5-ProAGG in the CSF sample an NSun2 gene.

6 . The method of claim 5 , wherein the level of the one or more 5-tRF is greater than the level of the 5-tRF in the comparator by at least three fold.

7 . The method of claim 5 , wherein the level of 5-tRF is determined by at least one of: (1) adding an RNA linker to the 5-tRFs and detecting with dye-based qRT-PCR, (2) melt curve qRT-PCR of the 5-tRF , or (3) probe-free qRT-PCR of the 5-tRF .

8 . The method of claim 5 , wherein the 5-tRF is not tRF5-LeuCAG.

9 . A method of treating Alzheimer's Disease (AD) in a human patient suspected of having AD, the method comprising:

obtaining a serum sample from the human patient,

determining a level of tRF5-ProAGG in the serum sample,

comparing the level of the tRF5-ProAGG in the serum sample with the level in a comparator sample that is a normal, control serum sample;

determining that the serum sample from the human patient has a decrease in tRF5-ProAGG; and

administering to the human patient having a decrease of tRF5-ProAGG in the serum sample an NSun2 gene.