Amyloid‐beta plasma and cerebrospinal fluid biomarkers in aged dogs with cognitive dysfunction syndrome

Abstract

Background Cognitive dysfunction syndrome (CDS) is a common progressive neurodegenerative disease that is poorly defined. Specific multitargeted protocols do not exist for setting the diagnosis and the prognosis of the syndrome. Hypothesis/Objectives To quantify Aβ42 and Aβ40 peptides in blood and cerebrospinal fluid (CSF) and to investigate their contribution to CCDS. Animals A total of 61 dogs from a hospital population. Methods Case‐control study. Six young (YG: 0‐4 years old), 8 middle‐aged (4‐8 years old), 17 cognitively unimpaired and aged (CU: 8‐20 years old), and 30 cognitively impaired and aged (CI: 8‐17 years). From the CI group, 10 dogs exhibited mild impairment (CI‐MCI) and 20 exhibited severe impairment (CI‐SCI). Cognitive status was assessed using a validated owner‐based questionnaire. Direct and indirect Aβ markers were determined in plasma fractions (total‐TP, free‐FP, bound to plasma components‐CP) and CSF using commercial ELISA assays (AΒtest, Araclon Biotech). Results TPAβ42/40 facilitated discrimination between CI‐MCI and CU aged dogs with area under curve ≥ 0.79. CSFAβ42 levels were higher ( P = .09) in CU (1.25 ± 0.28 ng/mL) than in MCI (1.04 ± 0.32 ng/mL) dogs. CSF Aβ42 levels were correlated with the CP fragment (CPAβ40: P = .02, CPAβ42: P = .02). CPAβ42 was higher in the CI‐MCI (23.03 ± 11.79 pg/μL) group compared to the other aged dogs (CU: 10.42 ± 7.18 pg/μL, P = .02, SCI: 11.40 ± 12.98 pg/μL, P = .26). Conclusion and Clinical Importance The Aβ should be determined in all of the 3 plasma fractions (TP, FP, CP). In the clinical approach, TPAβ42/40 could be used as an efficient preselection tool for the aged canine population targeting dogs with mild cognitive impairment.

Protein profiling and assessment of amyloid beta levels in plasma in canine refractory epilepsy

“…The mean plasma Aβ 42 level with refractory idiopathic epilepsy was significantly greater levels when compared to normal dogs (99 pg/ mL vs. 5.9 pg/mL, p < 0.05, Figure 1). Similarly, it was observed that dogs with cognitive impairment exhibited increased levels of plasma Aβ 42 (31,32,34).…”

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 ].…”

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).…”

“…With the extended lifespan of companion animals, the importance of CCDS, a representative geriatric disease, is increasing. However, accurate treatments remained elusive until recently (14). Various therapeutic approaches have been reported to enhance cognitive abilities and improve quality of life (3).…”