Sirtuin (SIRT) pathway has a crucial role in Alzheimer’s disease (AD). The present study evaluated the alterations in serum sirtuin1 (SIRT1) concentration in healthy individuals (young and old) and patients with AD and mild cognitive impairment (MCI). Blood samples were collected from 40 AD and 9 MCI patients as cases and 22 young healthy adults and 22 healthy elderly individuals as controls. Serum SIRT1 was estimated by Surface Plasmon Resonance (SPR), Western Blot and Enzyme Linked Immunosorbent Assay (ELISA). A significant (p<0.0001) decline in SIRT1 concentration was observed in patients with AD (2.27±0.46 ng/µl) and MCI (3.64±0.15 ng/µl) compared to healthy elderly individuals (4.82±0.4 ng/µl). The serum SIRT1 concentration in healthy elderly was also significantly lower (p<0.0001) compared to young healthy controls (8.16±0.87 ng/µl). This study, first of its kind, has demonstrated, decline in serum concentration of SIRT1 in healthy individuals as they age. In patients with AD and MCI the decline was even more pronounced, which provides an opportunity to develop this protein as a predictive marker of AD in early stages with suitable cut off values.

Summary: Frailty has emerged as a major health issue among older patients. A consensus on definition and diagnosis is yet to be achieved. Various biochemical abnormalities have been reported in frailty. Activation of sirtuins, a conserved family of NAD‐dependent proteins, is one of the many mimics of calorie restriction which improves lifespan and health in experimental animals. In this cross‐sectional study, we assessed the circulating sirtuin levels in 119 (59.5%) nonfrail and 81 (40.5%) frail individuals, diagnosed by Fried's criteria. Serum SIRT1, SIRT2, and SIRT3 were estimated by surface plasmon resonance (SPR) and Western blot. Serum sirtuins level in mean+SD; SIRT1 (nonfrail –4.67 ± 0.48 ng/μL; frail – 3.72 ± 0.48 ng/μL; P < 0.0001), SIRT2 (nonfrail – 15.18 ± 2.94 ng/μL; frail – 14.19 ± 2.66 ng/μL; P = 0.016), and SIRT3 (nonfrail‐7.72 ± 1.84 ng/μL; frail – 6.12 ± 0.97 ng/μL; P < 0.0001) levels were significantly lower among frail patients compared with the nonfrail. In multivariable regression analysis, lower sirtuins level were significantly associated with frailty after adjusting age, gender, diabetes mellitus, hypertension, cognitive status (Mini Mental State Examination scores) and number of comorbidities. For detecting the optimum diagnostic cutoff value a ROC analysis was carried out. The area under curve for SIRT1 was 0.9037 (cutoff – 4.29 ng/μL; sensitivity – 81.48%; specificity – 79.83%) and SIRT3 was 0.7988 (cutoff – 6.61 ng/μL; sensitivity – 70.37%; specificity – 70.59%). This study shows that lower circulating SIRT1 and SIRT3 levels can be distinctive marker of frailty.

The elevated level of cerebrospinal fluid (CSF) Tau and phosphorylated Tau₁₈₁ (p-Tau₁₈₁) proteins are well established hallmarks of Alzheimer’s disease (AD). Elevated level of p-Tau₁₈₁ can differentiate AD from other neurodegenerative disease. However, the expression level of these proteins in serum of AD patient is not well set up. This study sought to evaluate the level of Tau and p-Tau₁₈₁ in serum of AD, and mild cognitive impairment (MCI) patients for an alternative approach to establish protein-based markers by convenient way. Blood samples were collected from 39 AD patients, 37 MCI patients and 37 elderly individuals as controls. The levels of Tau and p-Tau₁₈₁ in the serum of the different groups were measured by label free real time Surface Plasmon Resonance technology by using specific antibodies, and were further confirmed by the conventional western blot method. An appropriate statistical analysis, including Receiver Operating Characteristic (ROC), was performed. The concentrations of serum Tau and p-Tau₁₈₁ were significantly higher (p<0.00001) in AD (Tau; 47.49±9.00ng/μL, p-Tau₁₈₁; 0.161±0.04 ng/μL) compared to MCI (Tau; 39.26±7.78 ng/μL, p-Tau₁₈₁; 0.135±0.02 ng/μL) and were further higher compared to elderly controls (Tau; 34.92±6.58 ng/μL, p-Tau₁₈₁; 0.122±0.01 ng/ μL). A significant (p<0.0001) downhill correlation was found between Tau as well as p-Tau₁₈₁ levels with HMSE and MoCA score. This study for the first time reports the concentration of Tau and p-Tau₁₈₁ in serum of AD and MCI patients. The cutoff values of Tau and p-Tau₁₈₁ of AD and MCI patients with sensitivity and specificity reveal that serum level of these proteins can be used as a predictive marker for AD and MCI.