β-amyloid beta peptides (Aβ1-42) are predominant components of amyloid plaques in brains of patients with Alzheimer’s disease (AD). It is believed that Aβ1-42 accumulation induces microglia to secrete neurotoxins leading to neuronal death. Microglial activation has been shown to occur at early stage of AD. Therefore, it may be a suitable biomarker for early AD compared with Aβ1-42 and phosphorylated tau. The objective of this study was to determine differential expression of microglial secretory proteins induced by Aβ1-42 compared with that of control using 1D LC-MS/MS. Proteins that were secreted from Aβ1-42-induced microglia at 12 h were separated on SDS-PAGE. Each band was tryptic digested followed by LC-MS/MS analysis. Obtained amino acid sequences were searched in NCBInr database for protein identification. The result showed that induction with Aβ1-42 altered microglial secretory proteins. Moreover, differential expressions of 46 candidate proteins induced by Aβ1-42 were identified. These proteins were classified according to their functions as followed: regulation of gene expression, cell communication/signal transduction, cellular transport, cytoskeletal structural integrity, metabolism, immune response/inflammation, heme association and protease inhibitor. Among these proteins, 14 candidate proteins involved mild cognitive impairment. These results indicated that Aβ1-42 induced a broad spectrum response in microglia related to pathogenesis of early AD. These proteins may apply to be early AD biomarkers.