BackgroundThe data that we gathered from a protein-protein interaction (PPI) prediction tool, FpClass, and a limited number of studies indicated that the chaperones HSP90AA1, HSPA4, STUB1/CHIP might interact with amyloid-β (Aβ) and/or tau and could subsequently be co-released into the cerebrospinal fluid (CSF). Therefore, we investigated CSF levels of HSP90AA1, HSPA4, and STUB1/CHIP in Alzheimer's disease (AD), Non-AD mild cognitive impairment (Non-AD MCI), and frontotemporal dementia (FTD) cases.MethodsThe CSF levels of HSP90AA1, HSPA4, STUB/CHIP, and core AD biomarkers were determined by ELISA in AD (n = 90), Non-AD MCI (n = 27), FTD (n = 15), and subjective cognitive impairment (SCI) (n = 20) subjects.ResultsHSP90AA1 levels were significantly higher in AD cases compared to the SCI subjects. The CSF levels of STUB1/CHIP were significantly lower in AD, Non-AD MCI and FTD cases compared to the SCI subjects. STUB1/CHIP levels of FTD cases were significantly lower than all other groups. HSPA4 levels was correlated with core AD biomarkers (Aβ 1-42, p-Tau, t-Tau) regardless of disease. Non-