Salivary Biomarkers for Alzheimer’s Disease and Related Disorders

Abstract

The search for accessible and cost-effective biomarkers to complement current cerebrospinal fluid (CSF) and imaging biomarkers in the accurate detection of Alzheimer disease (AD) and other common neurodegenerative disorders remains a challenging task. The advances in ultra-sensitive detection methods has highlighted blood biomarkers (e.g. amyloidb and neurofilament light) as a valuable and realistic tool in a diagnostic or screening process. Saliva, however, is also a rich source of potential biomarkers for disease detection and offers several practical advantages over biofluids that are currently examined for neurodegenerative disorders. However, while this may be true for the general population, challenges in collecting saliva from an elderly population should be seriously considered. In this review, we begin by discussing how saliva is produced and how age-related conditions can modify saliva production and composition. We then focus on the Enhanced digital features To view enhanced digital features for this article go to https://doi.org/10.6084/ m9.figshare.9792335.

Body Fluid Biomarkers for Alzheimer’s Disease—An Up-To-Date Overview

“…Therefore, due to the capacity of molecules to pass from the blood to the saliva through passive diffusion, active transport or microfiltration, saliva is a promising AD-related biomarker pool that could be used for its early and accurate diagnosis [ 147 , 148 ]. The most important AD biomarkers found within the saliva are Aβ peptides, T-tau and P-tau, acetylcholine, lactoferrin, and trehalose, each related to different AD pathophysiological mechanism.…”

“…Owing to the saliva–blood interactions and the buccal cell degradation, Aβ peptides should also be present in the saliva, as APP is a widely expressed protein in the peripheral tissues. Although the number of studies on the matter is still considerably limited, recent results have shown that salivary Aβ 42 is increased in AD patients, while Aβ 40 does not change [ 148 , 149 , 150 ]. However, there are no studies regarding the Aβ 42 /Aβ 40 ratio in the saliva, which should also be validated considering its significant relevance in the CSF [ 151 ].…”

“…Therefore, lactoferrin has been associated with AD pathogenesis, as it has been detected in the amyloid plaques, NFTs and microglia of AD brains [ 164 , 165 ]. Studies on AD patients are still limited, but there is strong evidence that the salivary levels of lactoferrin significantly decrease when compared to healthy controls and elderly subjects [ 139 , 148 , 164 , 168 ]. Moreover, lactoferrin has also demonstrated its potential for early disease detection, as the accuracy of AD diagnosis using it was greater than with CSF T-tau and Aβ42 [ 139 , 151 ].…”

The Potential Role of SARS-COV-2 in the Pathogenesis of Parkinson's Disease

“…Current evidence suggests different pathogens as triggers of a cerebral chronic neuroinflammatory response (66,67); αsynuclein is involved in important aspects of immune activation, specifically with the innate immune response. It may have a regulatory role in the immune response of peripheric and central neurons (68)(69)(70) and could be involved in the canonic activation of inflammatory pathways (inflammation), as well as the chronic immune response and neurotoxicity (neurodegeneration) (71). This occurs due to the overexpression of Toll-like receptors (TLR) and Nuclear Factor (NF-κB), activating, in turn, the cytokine response cascade.…”

Peripheral Biomarkers for Alzheimer’s Disease: Update and Progress

“…In the second contribution, Ashton et al [8] review the use of saliva as a peripheral biospecimen. Our group has shown that Aβ was detectable and elevated in the saliva of AD subjects [9].…”