Early detection and monitoring of neurodegenerative diseases using a multidisease diagnostic platform

A method for detecting the presence of Parkinson's Disease (PD)-related pathology in a subject with early-stage PD, the method comprising:

• (a) obtaining an immunoglobulin-containing biological sample from the subject;
• (b) providing a protein target set comprising protein targets MARK1, PUSL1, IL20, CCL19, and anti-human anti-IgG kappa light chain antibody, and/or epitope binding fragments thereof, wherein the protein targets and/or epitope binding fragments thereof are attached to a substrate,
• (c) contacting the biological sample with the protein target set under conditions under which each of MARK1, PUSL1, IL20, CCL19, or epitope binding fragments thereof, forms an immunocomplex with a corresponding PD-related autoantibody biomarker if present in the biological sample, and the anti-human anti-IgG kappa light chain antibody forms immunocomplexes with all IgG antibodies having a kappa light chain in the biological sample;
• (d) adding a detectable label to the immunocomplexes such that the immunocomplexes are labeled;
• (e) measuring the levels of the labeled immunocomplexes to generate levels of PD-related autoantibody biomarkers and a total IgG antibody level in the biological sample;
• (f) analyzing at least one covariate of the subject to generate covariate data;
• and
• (g) determining an PD score for the subject by:
• (A) inputting the levels of the subject's PD autoantibody biomarker, total IgG antibody level, and the covariate data into a classification algorithm configured to (1) determine therefrom an PD score, and (2) output the PD score.

A kit for detecting the presence of AD-related pathology in a subject, the kit comprising:

• (a) a protein target set comprising protein targets MGC31944 or MGC31936, HSH2D, GCDH, CCL19, LGALS1 (Galectin-1), DNAJC8, ICAM-4, and anti-human anti-IgG kappa light chain antibody, and/or epitope binding fragments thereof, wherein the protein targets and/or epitope binding fragments thereof are attached to a substrate comprising a plurality of beads, each bead attached to only one type of protein target, and/or epitope binding fragment thereof, of the protein targets,
• (b) a multi-well plate wherein each well of the multi-well plate contains a bead mix and a portion of the plurality of beads that are each attached to only one type of protein target, and/or epitope binding fragment thereof, of the protein targets, wherein each protein target, and/or epitope binding fragment thereof, is represented in each well of the multi-well plate;
• (c) at least one control;
• and
• (d) assay reagents for detection of:
• i) immunocomplexes formed by binding of each protein target or epitope binding fragment thereof to a corresponding AD-related autoantibody if present in the subject's immunoglobulin-containing biological sample, and ii) immunocomplexes formed by binding of the anti-human anti-IgG kappa light chain antibody to all IgG antibodies having a kappa light chain in the subject's biological sample,
• wherein the assay reagents comprise a detectable label for labeling the formed immunocomplexes.

A kit for detecting the presence of PD-related pathology in a subject with early-stage PD, the kit comprising:

• (a) a protein target set comprising protein targets MARK1, PUSL1, IL20, CCL19, and anti-human anti-IgG kappa light chain antibody, and/or epitope binding fragments thereof, wherein the protein targets and/or epitope binding fragments thereof are attached to a substrate comprising a plurality of beads, each bead attached to only one type of protein target, and/or epitope binding fragment thereof, of the protein targets,
• (b) a multi-well plate wherein each well of the multi-well plate contains a bead mix and a portion of the plurality of beads that are each attached to only one type of protein target, and/or epitope binding fragment thereof, of the protein targets, wherein each protein target, and/or epitope binding fragment thereof, is represented in each well of the multi-well plate;
• (c) at least one control;
• and
• (d) assay reagents for detection of:
• i) immunocomplexes formed by binding of each protein target or epitope binding fragment thereof to a corresponding PD-related autoantibody biomarker if present in the subject's immunoglobulin-containing biological sample, and ii) immunocomplexes formed by binding of the anti-human anti-IgG kappa light chain antibody to all IgG antibodies having a kappa light chain in the subject's biological sample,
• wherein the assay reagents comprise a detectable label for labeling the formed immunocomplexes.

A kit for detecting the presence of AD-related pathology in a subject, the kit comprising:

• (a) a protein target set comprising protein targets MGC31944 or MGC31936, HSH2D, GCDH, CCL19, LGALS1 (Galectin-1), DNAJC8, ICAM-4, and anti-human anti-IgG kappa light chain antibody, and/or epitope binding fragments thereof, wherein the protein targets and/or epitope binding fragments thereof are attached to a substrate comprising a microfluidics device,
• (b) at least one control;
• and
• (c) assay reagents for detection of:
• i) immunocomplexes formed by binding of each protein target or epitope binding fragment thereof to a corresponding AD autoantibody biomarker if present in the subject's immunoglobulin-containing biological sample, and ii) immunocomplexes formed by binding of the anti-human anti-IgG kappa light chain antibody to all IgG antibodies having a kappa light chain in the subject's biological sample,
• wherein the assay reagents comprise a detectable label for labeling the formed immunocomplexes.

A kit for detecting the presence of PD-related pathology in a subject with early-stage PD, the kit comprising:

• (a) a protein target set comprising protein targets MARK1, PUSL1, IL20, CCL19, and anti-human anti-IgG kappa light chain antibody, and/or epitope binding fragments thereof, wherein the protein targets and/or epitope binding fragments thereof are attached to a substrate comprising a microfluidics device,
• (b) at least one control;
• and
• (c) assay reagents for detection of:
• i) immunocomplexes formed by binding of each protein target or epitope binding fragment thereof to a corresponding PD-related autoantibody if present in the subject's immunoglobulin-containing biological sample, and ii) immunocomplexes formed by binding of the anti-human anti-IgG kappa light chain antibody to all IgG antibodies having a kappa light chain in the subject's biological sample,
• wherein the assay reagents comprise a detectable label for labeling the formed immunocomplexes.