Sirtuin1: A Promising Serum Protein Marker for Early Detection of Alzheimer’s Disease

Abhay K Singh,Abhishek Gupta,Rahul Kumar,Manjari Tripathi,Prakash K Sharma,Prasun Chaterjee,Aparajit B Dey,Kamaldeep Gill,Sharmistha Dey,Elliot Mufson

doi:10.1371/journal.pone.0061560

Abhay K Singh, Abhishek Gupta + Show 8 more

Open Access

https://doi.org/10.1371/journal.pone.0061560

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Journal: PLoS ONE	Publication Date: Apr 16, 2013
Citations: 147	License type: CC BY 4.0

Affiliation: All India Institute of Medical Sciences

Abstract

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.

Highlights

Alzheimer’s disease (AD), a neurodegenerative disease and leading cause of dementia, has emerged as a major public health challenge for ageing populations all over the world
It has been reported that SIRT1 increases the expression of ADAM10 gene encoding a secretase which protects against accumulation of pathogenic Ab peptide [8]
mild cognitive impairment (MCI) was diagnosed in patients with memory complaints and Mental State Examination scale (MMSE) scores above 24 with normal Clinical Dementia Rating Scale and the Blessed Dementia Rating Scale but abnormalities in memory domain of Wechsler Adult Intelligence Scale (WAIS), Rey-Osterrieth Complex Figure for visuospatial competence and auditory visual learning tests

Summary

Introduction

Alzheimer’s disease (AD), a neurodegenerative disease and leading cause of dementia, has emerged as a major public health challenge for ageing populations all over the world. The poor understanding of the pathogenesis of AD and consequent lack of definitive therapy provides opportunity for development of newer diagnostic and treatment strategies. In this scenario recent studies have indicated a possible mechanism involving the sirtuin proteins which may have diagnostic and therapeutic potential in AD. Among them SIRT1 is well characterized and is considered to be responsible for delaying the process of ageing in animal models [3]. Against AD in transgenic mouse model over-expressing SIRT1, has been reported [7]. It has been reported that SIRT1 increases the expression of ADAM10 gene encoding a secretase which protects against accumulation of pathogenic Ab peptide [8]

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