Salivary gland dysfunction and salivary redox imbalance in patients with Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is associated with the deposition of β-amyloid in the brain. AD accounts for over 50% of cases of dementia which results from disturbances in redox homeostasis. Indeed, increased intensity of protein oxidation and nitration as well as lipid peroxidation is observed in brain areas with considerable amounts of amyloid plaques and neurofibrillary tangles. However, little is known about the oxidoreductive balance of salivary glands in AD patients. Therefore, the aim of this study was to evaluate the antioxidant barrier and oxidative/nitrosative stress biomarkers in stimulated saliva and blood of AD patients. The study was participated by 25 AD patients and 25 non-demented controls without neurological diseases or cognitive impairment, matched by age and gender to the study group. The number of patients was determined based on a previous pilot study (test power = 0.9). We found a significant decrease in the activity of erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GPx), increased activity of catalase (CAT) and reduced concentration of plasma non-enzymatic antioxidants (uric acid, UA and reduced glutathione, GSH). In contrast, in the stimulated saliva of AD patients we observed significantly decreased activity of all antioxidant enzymes (SOD, CAT and GPx) as well as concentration of GSH compared to the control group. The content of lipid (malondialdehyde, MDA) and protein (advanced oxidation protein products, AOPP; advanced glycation end-products, AGE) oxidation products as well as biomarkers of nitrosative stress (peroxynitrite, nitrotyrosine) was significantly higher in both saliva and plasma of AD patients compared to the controls. In AD patients, we also observed a considerable decrease in stimulated saliva secretion and salivary total protein content, and an increase in salivary β-amyloid concentration. In conclusion, AD results in redox imbalance towards oxidative reactions, both at the level of the oral cavity and the entire body. General redox balance disturbances do not coincide with salivary redox balance disturbances. Reduction in stimulated saliva secretion in AD patients reflects secretory dysfunction of the parotid glands.

Ordering Knowledge in the Markers of Psychiatric/Mental Disorders

“…However, other studies of serum proteins found that the serum YKL-40 was the only protein (of Aβ42/Aβ40, YKL-40, and t-tau) that was still higher in vascular dementia patients even after 4 weeks of hospital treatment, suggesting the usefulness of YKL-40 for vascular dementia diagnostics [39]. These dementia markers are also immune-related proteins and co-occur with oxidative stress damage, even in saliva [40]. Another study found higher d-serine levels in the serum and cerebrospinal fluid (CSF) of persons suffering from AD [41].…”

Oxidation, Glycation, and Carbamylation of Salivary Biomolecules in Healthy Children, Adults, and the Elderly: Can Saliva Be Used in the Assessment of Aging?

“…Increased deposition of protein glycoxidation products was found in the brains of patients with Alzheimer’s disease and Parkinson’s disease. 8 , 38 , 67 , 71–74 Thus, further studies are needed on the use of saliva to evaluate the aging of the central nervous system.…”

Differentially Aquaporin 5 Expression in Submandibular Glands and Cerebral Cortex in Alzheimer’s Disease

“…Numerous scientific publications indicate that AD patients have systemic manifestations accompanying nervous system dysfunction, which suggests that the disease affects both the brain and peripheral organs, including the salivary glands [ 8 , 9 , 10 , 39 ]. Salivary gland dysfunction in AD patients was associated with salivary redox imbalance linked with chronic inflammation [ 10 ]. Recently, it has been described as a hypothetical mechanism for LPS-induced downregulation of AQP5 [ 40 ].…”

“…A number of studies indicates that patients with AD have systemic manifestations accompanying nervous system dysfunction, which suggests that the disease affects both the brain and the peripheral organs. Several studies have reported changes in the function and morphology of salivary glands in AD [ 7 , 8 , 9 , 10 ]. Saliva is a biofluid produced mainly by three pairs of major salivary glands, the submandibular, parotid, and sublingual glands [ 11 ].…”