Change in the plasma proteome associated with canine cognitive dysfunction syndrome (CCDS) in Thailand

Abstract

Background Canine cognitive dysfunction syndrome (CCDS) is a progressive neurodegenerative disorder found in senior dogs. Due to the lack of biological markers, CCDS is commonly underdiagnosed. The aim of this study was to identify potential plasma biomarkers using proteomics techniques and to increase our understanding of the pathogenic mechanism of the disease. Plasma amyloid beta 42 (Aβ42) has been seen to be a controversial biomarker for CCDS. Proteomics analysis was performed for protein identification and quantification. Results Within CCDS, ageing, and adult dogs, 87 proteins were identified specific to Canis spp. in the plasma samples. Of 87 proteins, 48 and 41 proteins were changed in the ageing and adult groups, respectively. Several distinctly expressed plasma proteins identified in CCDS were involved in complement and coagulation cascades and the apolipoprotein metabolism pathway. Plasma Aβ42 levels considerably overlapped within the CCDS and ageing groups. In the adult group, the Aβ42 level was low compared with that in the other groups. Nevertheless, plasma Aβ42 did not show a correlation with the Canine Cognitive Dysfunction Rating scale (CCDR) score in the CCDS group (p = 0.131, R2 = 0.261). Conclusions Our present findings suggest that plasma Aβ42 does not show potential for use as a diagnostic biomarker in CCDS. The nano-LC-MS/MS data revealed that the predictive underlying mechanism of CCDS was the co-occurrence of inflammation-mediated acute phase response proteins and complement and coagulation cascades that partly functioned by apolipoproteins and lipid metabolism. Some of the differentially expressed proteins may serve as potential predictor biomarkers along with Aβ42 in plasma for improved CCDS diagnosis. Further study in larger population-based cohort study is required in validation to define the correlation between protein expression and the pathogenesis of CCDS.

Characterization of the plasma proteome from healthy adult dogs

“…Although proteomic analysis of canine plasma is less performed than serum analysis, some studies on canine plasma have been reported, with the plasma proteins detected in dogs with SIRS and MODS being 68, 12 in obese dogs with and without obesity-related metabolic dysfunction, and nally 87 in dogs diagnosed with canine cognitive dysfunction syndrome respectively. (Kuleš et al, 2016;Tvarijonaviciute et al, 2016;Phochantachinda et al, 2021).…”

Successful and Unsuccessful Brain Aging in Pets: Pathophysiological Mechanisms behind Clinical Signs and Potential Benefits from Palmitoylethanolamide Nutritional Intervention

“…Routine blood tests in elderly dogs would show a mild increase of liver enzymes [31], with no other salient abnormalities being definitely confirmed to date. In canine patients with CDS, detection and quantification of soluble oligomers of β-amyloid fragments 1-40 and 1-42, hyperphosphorylated tau protein, and neurofilament light chain are considered promising, although not yet validated, blood biomarkers [31,32,[61][62][63][64][65].…”

“…The pharmacological potential of um-PEA in controlling neuroinflammation-either singly or co-ultramicronized with the antioxidant luteolin (i.e., co-ultra PEA)-has been proven by numerous investigations in various models of neurodegenerative conditions and senile dementia, both in vitro and in vivo [241][242][243][244][245]. In rat hippocampal slices and neuroblastoma cells challenged with β-amyloid 1-42, PEA in the ultramicronized or coultramicronized formulation exhibited anti-inflammatory and anti-apoptotic effects, as well as the ability to decrease the expression of markers of oxidative stress and astroglial injuries, such as iNOS and GFAP [65,126]. In rats that received an intrahippocampal infusion of β-amyloid 1-42, chronic treatment for 14 days with co-ultra PEA prevented astrocyte hypertrophy as well as the production of pro-inflammatory cytokines and enzymes, compared to vehicle-treated animals [246].…”

Non-Controlled Clinical Efficacy Study Following Brain Six Complex Extractⓒ Administration in Dogs with Cognitive Dysfunction Syndrome

“…The prevalence of CCDS is up to 60% in dogs, predominantly >11 years; however, the actual diagnosis rate remains quite low, at approximately 2% (5,12,14). Species-specific differences in CCDS have not been identified (12).…”

“…The prevalence of CCDS is up to 60% in dogs, predominantly >11 years; however, the actual diagnosis rate remains quite low, at approximately 2% (5,12,14). Species-specific differences in CCDS have not been identified (12). The major clinical signs of CCDS include apparent confusion, anxiety, disturbance of the sleep/wake cycle, and decreased interactions between pets and their owners (3).…”