TY - JOUR
T1 - Blood Circulatory Level of Seven Sirtuins in Alzheimer’s Disease
T2 - Potent Biomarker Based on Translational Research
AU - Pradhan, Rashmita
AU - Singh, Abhinay Kumar
AU - Kumar, Pramod
AU - Bajpai, Swati
AU - Pathak, Mona
AU - Chatterjee, Prasun
AU - Dwivedi, Sadanand
AU - Dey, A. B.
AU - Dey, Sharmistha
N1 - Funding Information:
This work was supported by All India Institute of Medical Sciences, New Delhi, providing funds for procurement of equipment and consumables.
Funding Information:
The authors acknowledged all the study participants and Indian Council of Medical Research for proving the fellowship to Rashmita Pradhan.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2022/3
Y1 - 2022/3
N2 - Alzheimer’s disease (AD) is an accelerating neurodegenerative disorder. Dysfunction of mitochondria and oxidative stress contributes to the pathogenesis of AD. Sirtuins play a role in this pathway and can be a potential marker to study neurodegenerative changes. This study evaluated serum levels of all seven sirtuin (SIRT1–SIRT7) proteins in three study groups: AD, mild cognitive impairment (MCI) and geriatric control (GC) by surface plasmon resonance (SPR) technique. Further, it was validated by the Western blot experiment. ROC analysis was performed to differentiate the study group based on the concentration of serum SIRT proteins. Out of seven sirtuins, serum SIRT1, SIRT3 and SIRT6 levels (mean ± SD) were significantly decreased in AD (1.65 ± 0.56, 3.15 ± 0.28, 3.36 ± 0.32 ng/µl), compared to MCI (2.17 ± 0.39, 3.60 ± 0.51, 3.73 ± 0.48 ng/µl) and GC (2.84 ± 0.47, 4.55 ± 0.48, 4.65 ± 0.55 ng/µl). ROC analysis showed the cut-off value with high sensitivity and specificity for cognitive impairment (AD and MCI). The concentration declined significantly with the disease progression. No specific difference was observed in the case of other SIRTs between the study groups. This study reveals an inverse relation of serum SIRT1, SIRT3 and SIRT6 concentration with AD. ROC analysis showed that these serum proteins have greater accuracy in diagnosing of AD. This is the first report of estimation of all seven serum sirtuins and the clinical relevance of SIRT3 and SIRT6 as serum protein markers for AD.
AB - Alzheimer’s disease (AD) is an accelerating neurodegenerative disorder. Dysfunction of mitochondria and oxidative stress contributes to the pathogenesis of AD. Sirtuins play a role in this pathway and can be a potential marker to study neurodegenerative changes. This study evaluated serum levels of all seven sirtuin (SIRT1–SIRT7) proteins in three study groups: AD, mild cognitive impairment (MCI) and geriatric control (GC) by surface plasmon resonance (SPR) technique. Further, it was validated by the Western blot experiment. ROC analysis was performed to differentiate the study group based on the concentration of serum SIRT proteins. Out of seven sirtuins, serum SIRT1, SIRT3 and SIRT6 levels (mean ± SD) were significantly decreased in AD (1.65 ± 0.56, 3.15 ± 0.28, 3.36 ± 0.32 ng/µl), compared to MCI (2.17 ± 0.39, 3.60 ± 0.51, 3.73 ± 0.48 ng/µl) and GC (2.84 ± 0.47, 4.55 ± 0.48, 4.65 ± 0.55 ng/µl). ROC analysis showed the cut-off value with high sensitivity and specificity for cognitive impairment (AD and MCI). The concentration declined significantly with the disease progression. No specific difference was observed in the case of other SIRTs between the study groups. This study reveals an inverse relation of serum SIRT1, SIRT3 and SIRT6 concentration with AD. ROC analysis showed that these serum proteins have greater accuracy in diagnosing of AD. This is the first report of estimation of all seven serum sirtuins and the clinical relevance of SIRT3 and SIRT6 as serum protein markers for AD.
KW - Alzheimer’s disease
KW - Mild cognitive impairment
KW - Protein marker
KW - Sirtuins
KW - SPR
UR - http://www.scopus.com/inward/record.url?scp=85122483822&partnerID=8YFLogxK
U2 - 10.1007/s12035-021-02671-9
DO - 10.1007/s12035-021-02671-9
M3 - Article
C2 - 34993847
AN - SCOPUS:85122483822
SN - 0893-7648
VL - 59
SP - 1440
EP - 1451
JO - Molecular Neurobiology
JF - Molecular Neurobiology
IS - 3
ER -