Cerebrospinal fluid HSP90AA1, HSPA4, and STUB1/CHIP levels in Alzheimer's disease, mild cognitive impairment, and frontotemporal dementia

SORDU P., ALAYLIOĞLU M., Samancı B., Bulu E., Güleç Z. E. K., BİLGİÇ B., ...Daha Fazla

Journal of Alzheimer's Disease, cilt.105, sa.2, ss.481-493, 2025 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 105 Sayı: 2
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1177/13872877251329540
  • Dergi Adı: Journal of Alzheimer's Disease
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, CINAHL, MEDLINE, Psycinfo, Veterinary Science Database
  • Sayfa Sayıları: ss.481-493
  • Anahtar Kelimeler: Alzheimer's disease, APOE, biomarker, cerebrospinal fluid, chaperone, heat shock protein, molecular chaperone, STUB1/CHIP chaperone protein
  • İstanbul Üniversitesi Adresli: Evet

Özet

Background: The 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. Methods: The 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. Results: HSP90AA1 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-APOE ε4 carrier FTD cases also had significantly lower STUB1/CHIP levels than other groups. Conclusions: The STUB1/CHIP holds promise as a potential biomarker for distinguishing between SCI subjects, AD, and FTD. Furthermore, APOE might serve as an additional discriminatory factor that might be integrated with this chaperone for enhanced discrimination.