Non-Invasive Nasal Discharge Fluid and Other Body Fluid Biomarkers in Alzheimer’s Disease

Abstract

The key to current Alzheimer’s disease (AD) therapy is the early diagnosis for prompt intervention, since available treatments only slow the disease progression. Therefore, this lack of promising therapies has called for diagnostic screening tests to identify those likely to develop full-blown AD. Recent AD diagnosis guidelines incorporated core biomarker analyses into criteria, including amyloid-β (Aβ), total-tau (T-tau), and phosphorylated tau (P-tau). Though effective, the accessibility of screening tests involving conventional cerebrospinal fluid (CSF)- and blood-based analyses is often hindered by the invasiveness and high cost. In an attempt to overcome these shortcomings, biomarker profiling research using non-invasive body fluid has shown the potential to capture the pathological changes in the patients’ bodies. These novel non-invasive body fluid biomarkers for AD have emerged as diagnostic and pathological targets. Here, we review the potential peripheral biomarkers, including non-invasive peripheral body fluids of nasal discharge, tear, saliva, and urine for AD.

Alteration of Neural Network and Hippocampal Slice Activation through Exosomes Derived from 5XFAD Nasal Lavage Fluid

“…Considering the same volume loaded onto the grid, the exosome density was higher in 5XFAD mice than that in control mice, as confirmed by a 3.2-fold increase in CD63 exosome marker expression levels ( Figure 1 E,F). Overall, the secretion of NLF-derived exosomes was enhanced in the AD animal model, similar to other body fluids [ 12 , 20 ]. After the concentration normalization, the neural network in the HD-MEA was measured for both neuronal cultures and organotypic hippocampal slice cultures (OHSCs) with the harvested intact exosomes ( Figure S1 ).…”

“…Given that olfactory dysfunction often precedes cognitive impairment in AD and overlaps anatomically with early AD-affected regions, the potential for applying nasal lavage fluid (NLF) as a non-invasive diagnostic tool is promising. NLF, generated by mucous membranes in the olfactory mucosa, serves to protect these sensory tissues while also potentially capturing the neuropathology unfolding in the surrounding system [ 12 ]. Therefore, exosomes obtained from this fluid could offer a snapshot of the ongoing state of neurodegeneration.…”

Alteration of neural network and hippocampal slice activation through exosomes derived from 5XFAD nasal lavage fluid

“…As such, other body fluid biomarkers are being investigated in sophisticated ways using tear, urine, sweat, saliva, and nasal lavage fluid (NLF) with relative ease compared to the invasive methods (Jeromin and Bowser 2017; Klyucherev et al 2022; Obrocki et al 2020; Teunissen et al 2022; Zetterberg and Bendlin 2021). It has been shown that NLF in particular contains amyloid precursor protein (APP) and α-synuclein reflecting the pathological changes that occur in AD, making it an efficient source of AD markers (Jung et al 2022; Kovacs et al 1996; Ohm and Braak 1987; Shi et al 2014; Yoo et al 2020). In the myriad of substances within NLF, exosomes are primarily categorized on the basis of their neuromodulatory effects on cellular interaction, synaptic plasticity, and signal transmissions (Ching and Kingham 2015; Frohlich et al 2014; Saeedi et al 2019; Sharma et al 2019; Thery et al 2002).…”