Cited 13 time in webofscience Cited 14 time in scopus

Serum Tau Proteins as Potential Biomarkers for the Assessment of Alzheimer's Disease Progression

Title
Serum Tau Proteins as Potential Biomarkers for the Assessment of Alzheimer's Disease Progression
Authors
Nam, EunjooLee, Yeong-BaeMoon, CheilChang, Keun-A
DGIST Authors
Moon, Cheil
Issue Date
2020-07
Citation
International Journal of Molecular Sciences, 21(14), 5007
Type
Article
Article Type
Article
Author Keywords
tau proteinserumAlzheimer&aposs diseasebiomarkerexosome
Keywords
PLASMA AMYLOID-BETACEREBROSPINAL-FLUIDDEMENTIANEURODEGENERATIONASSOCIATIONDIAGNOSISEXOSOMESCRITERIAPREDICTMEMORY
ISSN
1661-6596
Abstract
Total tau (t‐tau) and phosphorylated tau (p‐tau) protein elevations in cerebrospinal fluid (CFS) are well‐established hallmarks of Alzheimer’s disease (AD), while the associations of serum t‐tau and p‐tau levels with AD have been inconsistent across studies. To identify more accessible non‐invasive AD biomarkers, we measured serum tau proteins and associations with cognitive function in age‐matched controls (AMC, n = 26), mild cognitive impairment group (MCI, n = 30), and mild‐AD group (n = 20) according to the Mini‐mental State Examination (MMSE), Clinical Dementia Rating (CDR), and Global Deterioration Scale (GDS) scores. Serum t‐tau, but not p‐tau, was significantly higher in the mild‐AD group than AMC subjects (p < 0.05), and there were significant correlations of serum t‐tau with MMSE and GDS scores. Receiver operating characteristic (ROC) analysis distinguished mild‐AD from AMC subjects with moderate sensitivity and specificity (AUC = 0.675). We speculated that tau proteins in neuronal cell‐derived exosomes (NEX) isolated from serum would be more strongly associated with brain tau levels and disease characteristics, as these exosomes can penetrate the blood‐brain barrier. Indeed, ELISA and Western blotting indicated that both NEX t‐tau and p‐tau (S202) were significantly higher in the mild‐AD group compared to AMC (p < 0.05) and MCI groups (p < 0.01). In contrast, serum amyloid β (Aβ1–42) was lower in the mild‐AD group compared to MCI groups (p < 0.001). During the 4‐year follow‐up, NEX t‐tau and p‐tau (S202) levels were correlated with the changes in GDS and MMSE scores. In JNPL3 transgenic (Tg) mice expressing a human tau mutation, t‐tau and p‐tau expression levels in NEX increased with neuropathological progression, and NEX tau was correlated with tau in brain tissue exosomes (tEX), suggesting that tau proteins reach the circulation via exosomes. Taken together, our data suggest that serum tau proteins, especially NEX tau proteins, are useful biomarkers for monitoring AD progression. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
URI
http://hdl.handle.net/20.500.11750/12720
DOI
10.3390/ijms21145007
Publisher
MDPI AG
Related Researcher
  • Author Moon, Cheil Laboratory of Chemical Senses
  • Research Interests Brain convergent science based on chemical senses; olfaction; 감각신경계 기반 뇌융합과학; 후각 신경계
Files:
Collection:
Department of Brain and Cognitive SciencesLaboratory of Chemical Senses1. Journal Articles


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