Methods of diagnosing a synucleinopathy

A method of identifying a subject having a synucleinopathy, the method comprising determining the protein level of alpha-synuclein comprising a nitration of Y39, Y125, Y133, and/or Y136 in an alpha-synuclein protein in a CSF sample obtained from the subject, wherein the presence of nY39, nY125, nY133, and/or nY136 identifies the subject as having a synucleinopathy.

A method of diagnosing a synucleinopathy in a subject, the method comprising determining the protein level of alpha-synuclein comprising a nitration of Y39, Y125, Y133, and/or Y136 in an alpha-synuclein protein in a CSF sample obtained from the subject, wherein the presence of nY39, nY125, nY133, and/or nY136 identifies the subject as having a synucleinopathy.

A method of treating a subject having a synucleinopathy, the method comprising administering to the subject a therapeutically effective amount of a cognition-enhancing agent, an antidepressant agent, a dopamine promoter, an anti-tremor agent, and/or a neuroprotective agent, wherein the expression level of a nitrated alpha-synuclein protein having at least one of the following tyrosine residues Y39, Y125, Y133, and Y136 in an alpha-synuclein protein nitrated in a CSF sample obtained from the subject has been determined to be increased relative to a reference expression level of the at least one nitrated alpha-synuclein protein.

A method of treating a subject having a synucleinopathy, the method comprising:

• (a) determining the protein expression level of a nitrated alpha-synuclein protein comprising a nitration of Y39, Y125, Y133, and/or Y136 in an alpha-synuclein protein in a CSF sample obtained from the subject, wherein an increase in the expression level of the nitrated alpha-synuclein protein relative to a reference expression level identifies the subject as having a synucleinopathy;
• and
• (b) administering to the subject a therapeutically effective amount of a cognition-enhancing agent, an antidepressant agent, a dopamine promoter, an anti-tremor agent, and/or a neuroprotective agent.

A kit for diagnosing a synucleinopathy in a subject, the kit comprising:

• (a) probes or antibodies capable of determining the level of one or more of a nitrated alpha-synuclein protein in a CSF sample from the subject;
• and optionally
• (b) instructions for use of the probes or antibodies to determine the level of one or more nitrated alpha-synuclein protein in the CSF sample from the subject, wherein an increase in the level of one or more of the nitrated alpha-synuclein protein relative to a respective reference level indicates that the subject is likely to have a synucleinopathy.