An investigation of the correlation between the S-glutathionylated GAPDH levels in blood and Alzheimer's disease progression.

Chen Wei Tsai,Kuan Hung Lin,Cho Chen Hsieh,Chai Ching Lin,Muh Shi Lin,Chia Fan Tsai,Wei Jung Chen,Chongzhao Ran

doi:10.1371/journal.pone.0233289

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by two aggregates, namely, amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs) of hyperphosphorylated tau protein (tau-p), which are released into the blood in a very small amount and cannot be easily detected. An increasing number of recent studies have suggested that S-glutathionylated glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is highly correlated with Aβ in patients with AD and that S-glutathionylated GAPDH plays a role as a proapoptotic factor in AD. We found that S-glutathionylated GAPDH is abundant in the blood of AD patients, which is unusual because S-glutathionylated GAPDH cannot exist in the blood under normal conditions. The aim of this study was to further explore the correlation between the S-glutathionylated GAPDH levels in blood plasma and AD progression. As controls, we recruited 191 people without AD, which included 111 healthy individuals and 37 patients with depression and insomnia, in the psychosomatic clinic. Moreover, 47 patients with AD (aged 40–89 years) were recruited at the neurology clinic. The blood S-glutathionylated GAPDH levels in the AD patients were significantly (p < 0.001) higher (752.7 ± 301.7 ng/dL) than those in the controls (59.92 ± 122.4 ng/dL), irrespective of gender and age. For AD diagnosis, the criterion blood S-glutathionylated GAPDH level > 251.62 ng/dL exhibited 95.74% sensitivity and 92.67% specificity. In fact, the individuals aged 70–89 years, namely, 37 patients from the psychosomatic clinic and 42 healthy individuals, showed significant blood S-glutathionylated GAPDH levels (230.5 ± 79.3 and 8.05 ± 20.51 ng/dL, respectively). This finding might indicate neurodegenerative AD progression in psychosomatic patients and suggests that the degree of neuronal apoptosis during AD progression might be sensitively evaluated based on the level of S-glutathionylated GAPDH in blood.

Highlights

The majority of dementia cases can be diagnosed as Alzheimer’s disease (AD) [1], which is classified as a neurodegenerative disorder whose cause and progression are poorly understood
Some atypical cases of AD are diagnosed based on imaging studies comprising computed tomography (CT), magnetic resonance imaging (MRI), or the analysis of biomarkers in cerebrospinal fluid [7] obtained via lumbar puncture (LP)
The AUC was higher than 0.9, which indicated that the criterion blood Sglutathionylated glyceraldehyde 3-phosphate dehydrogenase (GAPDH) level > 251.62 ng/dL exhibited a high accuracy for the diagnosis of AD

Summary

Introduction

The majority of dementia cases can be diagnosed as AD [1], which is classified as a neurodegenerative disorder whose cause and progression are poorly understood. AD is diagnosed when patients present symptoms of memory loss at clinics, and most of these AD diagnoses are based on the results of clinical interviews and neuropsychological scores, such as the Cognitive Abilities Screening Instrument (CASI) [3], the Short Portable Mental State Questionnaire (SPMSQ) [4], the National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) [5], and the Mini-Mental State Examination (MMSE) [6] These scores do not accurately detect the early stages of dementia and do not distinguish between AD and vascular dementia.

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