Diagnostic biomarker profiles for the detection and diagnosis of alzheimer's disease
The present invention provides methods, compositions and kits for the detection of Alzheimer's disease (AD) diagnostic biomarkers, for the diagnosis of AD, for the identification of a subject at risk for developing AD, and for the generation of patient-specific AD diagnostic biomarker profiles.
1. A kit for detecting Alzheimer's disease (AD) diagnostic biomarkers in a subject's biological sample, the kit comprising:
(a) an ordered microarray comprising a substrate and autoantigens immobilized onto said substrate, wherein the only autoantigens in the microarray are the following:
a first group of autoantigens consisting of Pentatricopeptide repeat domain 2 (PTCD2); FERM domain containing 8 (FRMD8); Chromosome 9 open reading frame 9 (C9orf9); Lectin, galactoside-binding, soluble, 1 (galectin 1) (LGALS1); Proopiomelanocortin (adrenocorticotropin/beta-lipotropin/alpha-melanocyte stimulating hormone/beta-melanocyte stimulating hormone/beta-endorphin) (POMC), transcript variant 2; Mitogen-activated protein kinase-activated protein kinase 5 (MAPKAPK5), transcript variant 1; Centaurin, alpha 2 (CENTA2); DnaJ homolog subfamily C member 8; Ankyrin repeat and KH domain containing 1 (ANKHD1), transcript variant 3; Mitochondrial ribosomal protein L34 (MRPL34), and nuclear gene encoding mitochondrial protein; and
a second group of two or more autoantigens selected from the group consisting of hematopoietic SH2 domain containing (HSH2D); proteins corresponding to cDNA clone MGC:27152 IMAGE:4691630, complete cds; cDNA clone MGC:31944 IMAGE:4878869, complete cds; and cDNA clone MGC:32654 IMAGE:4701898, complete cds;
(b) assay reagents for label-based detection of at least three immunocomplexes formed by binding of the immobilized autoantigens of (a) to the AD diagnostic biomarkers in an immunoglobulin-containing biological sample from a subject; and
(c) a package labeling indicating a diagnosis of AD in said subject upon detecting:
1) formation of at least one immunocomplex from said first group of autoantigens: Pentatricopeptide repeat domain 2 (PTCD2); FERM domain containing 8 (FRMD8); Chromosome 9 open reading frame 9 (C9orf9); Lectin, galactoside-binding, soluble, 1 (galectin 1) (LGALS1); Proopiomelanocortin (adrenocorticotropin/beta-lipotropin/alpha-melanocyte stimulating hormone/beta-melanocyte stimulating hormone/beta-endorphin) (POMC), transcript variant 2; Mitogen-activated protein kinase-activated protein kinase 5 (MAPKAPK5), transcript variant 1; Centaurin, alpha 2 (CENTA2); DnaJ homolog subfamily C member 8; Ankyrin repeat and KH domain containing 1 (ANKHD1), transcript variant 3; Mitochondrial ribosomal protein L34 (MRPL34), and nuclear gene encoding mitochondrial protein; and
2) formation of two or more immunocomplexes from said second group of autoantigens: hematopoietic SH2 domain containing (HSH2D); proteins corresponding to cDNA clone MGC:27152 IMAGE:4691630, complete cds; cDNA clone MGC:31944 IMAGE:4878869, complete cds; and cDNA clone MGC:32654 IMAGE:4701898, complete cds.
2. The kit of claim 1 , wherein two or more autoantigens from said second group are selected from the group consisting of cDNA clone MGC:31944 IMAGE:4878869, complete cds; hematopoietic SH2 domain containing (HSH2D); and cDNA clone MGC:32654 IMAGE:4701898, complete cds.
3. The kit of claim 1 , wherein said package labeling indicates a diagnosis of AD upon positive detection of immunocomplexes from FERM domain containing 8 (FRMD8) and at least two autoantigens selected from the group consisting of cDNA clone MGC:31944 IMAGE:4878869, complete cds; hematopoietic SH2 domain containing (HSH2D); and cDNA clone MGC:32654 IMAGE:4701898, complete cds in said biological sample.
4. The kit of claim 1 , wherein said package labeling indicates a diagnosis of AD upon positive detection of immunocomplexes from FERM domain containing 8 (FRMD8); cDNA clone MGC:31944 IMAGE:4878869, complete cds; hematopoietic SH2 domain containing (HSH2D); and cDNA clone MGC:32654 IMAGE:4701898, complete cds in said biological sample.
5. The kit of claim 1 , wherein said package labeling indicates a diagnosis of AD upon positive detection of immunocomplexes from at least five autoantigens from said first group of autoantigens in said biological sample.
6. The kit of claim 1 , wherein said package labeling indicates a diagnosis of AD upon positive detection of immunocomplexes from ten autoantigens from said first group of autoantigens in said biological sample.