Determination of molecular chaperone levels in cerebrospinal fluids of Alzheimer’s patients

Background Molecular chaperones are a component of the protein homeostasis network and regulate the biogenesis, folding, and trafficking of proteins, protecting the proteome against misfolding, aggregation, and proteotoxicity [1]. Therefore, they serve as the first line of defense against toxicity caused by misfolded proteins such as Aβ and tau [2]. Amyloid precursor protein (APP) interacts with chaperones from the moments of microtubule‐associated protein tau (MAPT) production. These properties keep the molecular chaperones in close contact with many proteins within the cell, including proteins associated with Alzheimer’s disease (AD), such as APP and tau [3]. According to the data we obtained using the web‐based FpClass protein‐protein association (PPI) prediction program, which investigates protein‐protein interactions, we determined that the AD‐related proteins MAPT and APP strongly interact with the chaperone proteins HSP90AA1, CHIP (STUB1) and HSPA4. In light of this information, we thought these chaperone proteins could interact with Aβ and tau and exit the CSF together, and these chaperones could be used as a biomarker. Method Following this purpose, we determined the levels of HSP90AA1, STUB1, and HSPA4 chaperone proteins in CSF samples of AD, MCI, and FTD patients and individuals diagnosed with SCI using the ELISA method. Depending on the distribution of ApoE, any changes in CSF chaperone levels and co‐localization of these chaperones with MAPT and Aβ1‐42 were demonstrated by double‐immunofluorescence labeling in neuron‐differentiated human SH‐SY5Y cells. Within the scope of the study, these parameters included to be biomarkers that were investigated. Result CSF HSP90AA1 protein levels were increased in sporadic AD and FTD patients compared to controls, CSF HSPA4 protein levels were increased in sporadic AD patients compared to family history of AD patients, and CSF STUB1 protein levels were decreased in AD, MCI, and FTD patients compared to controls. Conclusion Considering the findings of our study, the presence of these chaperone proteins in CSF suggests that they may have an important place in the neuropathological processes of neurodegenerative diseases such as Alzheimer’s disease. The present work was supported by the Research Fund of Istanbul University‐Cerrahpasa. Project No. 33638