Dataset Information

Multiomics Profiling of Alzheimer’s Disease Serum for the Identification of Autoantibody Biomarkers

ABSTRACT: New biomarkers of Alzheimer’s Disease (AD) with diagnostic value in preclinical and prodromal stages are urgently needed. AD-related serum autoantibodies are potential candidate biomarkers. Here, we aimed at identifying AD-related serum autoantibodies using protein microarrays and mass spectrometry-based methods. To this end, an untargeted complementary screening using high-density (42,100 antigens) and low-density (384 antigens) planar protein-epitope signature tag (PrEST) arrays and an immunoprecipitation protocol coupled to mass spectrometry analysis were used for serum autoantibody profiling. From the untargeted screening phase, 377 antigens corresponding to 338 proteins were selected for validation. Out of them, IVD, CYFIP1 and ADD2 seroreactivity was validated using 128 sera from AD patients and controls by PrEST-suspension beads arrays, and ELISA or luminescence Halotag-based bead immunoassay using full-length recombinant proteins. Importantly, IVD, CYFIP1, and ADD2 showed in combination noticeable AD diagnostic ability. Moreover, IVD protein abundance in the prefrontal cortex was significantly two-fold higher in AD patients than in controls by WB and immunohistochemistry, whereas CYFIP1 and ADD2 were significantly down-regulated in AD patients. The panel of AD-related autoantigens identified by a comprehensive multiomics approach may provide new insights of the disease and should help in the blood-based diagnosis of Alzheimer’s disease.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

DISEASE(S): Alzheimer's Disease

SUBMITTER: Rodrigo Barderas

LAB HEAD: Rodrigo Barderas

PROVIDER: PXD028392 | Pride | 2021-12-20

REPOSITORIES: Pride

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Multiomics Profiling of Alzheimer's Disease Serum for the Identification of Autoantibody Biomarkers.

San Segundo-Acosta Pablo P Montero-Calle Ana A Jernbom-Falk August A Alonso-Navarro Miren M Pin Elisa E Andersson Eni E Hellström Cecilia C Sánchez-Martínez MariCruz M Rábano Alberto A Solís-Fernández Guillermo G Peláez-García Alberto A Martínez-Useros Javier J Fernández-Aceñero María Jesús MJ Månberg Anna A Nilsson Peter P Barderas Rodrigo R

Journal of proteome research 20211010 11

New biomarkers of Alzheimer's disease (AD) with a diagnostic value in preclinical and prodromal stages are urgently needed. AD-related serum autoantibodies are potential candidate biomarkers. Here, we aimed at identifying AD-related serum autoantibodies using protein microarrays and mass spectrometry-based methods. To this end, an untargeted complementary screening using high-density (42,100 antigens) and low-density (384 antigens) planar protein-epitope signature tag (PrEST) arrays and an immun ...[more]

PMID: 34628858

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			Action	DRS
	1BAD.msf	Msf
	1BAD.raw	Raw
	1BCTRL.msf	Msf
	1BCTRL.raw	Raw
	2BAD.msf	Msf