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

J Vet Intern Med. 2020 Jul;34(4):1532-1540. doi: 10.1111/jvim.15812. Epub 2020 Jun 18.

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.

Keywords: Alzheimer's; ELISA; biomarkers; canine; cerebrospinal fluid; dementia; diagnostic tool; plasma fragments.

MeSH terms

  • Aging
  • Amyloid beta-Peptides / blood*
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Animals
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Case-Control Studies
  • Cognitive Dysfunction / blood
  • Cognitive Dysfunction / cerebrospinal fluid
  • Cognitive Dysfunction / diagnosis*
  • Dog Diseases / blood
  • Dog Diseases / cerebrospinal fluid
  • Dog Diseases / diagnosis*
  • Dogs
  • Neurodegenerative Diseases / blood
  • Neurodegenerative Diseases / cerebrospinal fluid
  • Neurodegenerative Diseases / diagnosis
  • Neurodegenerative Diseases / veterinary*
  • Surveys and Questionnaires

Substances

  • Amyloid beta-Peptides
  • Biomarkers