Identification of Alzheimer's Disease Autoantibodies and Their Target Biomarkers by Phage Microarrays

The characterization of the humoral response in Alzheimer’s disease (AD) patients might aid in detecting the disease at early stages. We have combined phage display and protein microarrays to identify AD autoantibodies and their target biomarkers. After enrichment of the T7 phage display libraries from AD and healthy brain tissue mRNA in AD-specific phages, 1536 monoclonal phages were printed on microarrays to probe them with 8 AD and 8 healthy control sera. A total of 57 phages showed higher seroreactivity in AD. In total, 13 out of the 44 unique sequences displayed on the phages were selected for validation using 68 AD and 52 healthy control sera. Peptides from Anthrax toxin receptor 1, Nuclear protein 1, Glycogen phosphorylase, and Olfactory receptor 8J1 expressed in bacteria as HaloTag fusion proteins showed a statistically significant ability to discriminate between AD patients and controls. The identified panel of AD autoantibodies might provide new insights into the blood-based diagnosis of the disease.This work was supported by Grants SAF2014-53209-R to M.V. and R.B., Grant PI17CIII/00045 from the AES-ISCIII program to R.B., and Instituto de Salud Carlos III (ISCIII) cofounded by Fondo Europeo de Desarrollo Regional−FEDER for the Thematic Networks and Co-operative Research Centres: RIRAAF Network RD12/0013/0015 and ARADyAL (Grant RD16/0006/0014). We also gratefully acknowledge financial support from the Spanish Health Institute Carlos III (ISCIII) for Grants FIS PI17/01930 and CB16/12/00400. Fundacioń Solorzano Grant FS/38-2017 to M.F. The Proteomics Unit ́ belongs to ProteoRed, PRB3-ISCIII, supported by Grant PT17/0019/0023, of the PE I + D + I 2017-2020, funded by ISCIII and FEDER. P.S.S.-A.’s FPU predoctoral contract is supported by the Spanish Ministerio de Educacion, Cultura y ́ Deporte. A.M.-C. is supported by a predoctoral contract of the Fundacion Tatiana Perez de Guzman el Bueno