The invention provides a kit for detecting an Alzheimer autoantibody in serum. The kit comprises an antigen protein combination, the antigen protein combination contains at least four proteins, and the proteins are selected from RABPT5, RAGE, CRYAB, SRPK1, MAPT, MBP, PLP1, PTCD2, FRMD8, POMC, DNAJC8, CENTA2, HSP60, ADARB1, ASXL1, EDRK, GDF11, P21, CCL2, IL18, VEGF, LENG1 and MRPL34. The inventionfurther provides application of the limited antigen protein combination to preparation of a reagent for detection, diagnosis or risk prediction of Alzheimer, and methods for detection, diagnosis or risk prediction of Alzheimer.