title: Young to Middle-Aged Dogs with High Amyloid-β Levels in Cerebrospinal Fluid are Impaired on Learning in Standard Cognition tests.
abstract: Understanding differences in Alzheimer's disease biomarkers before the pathology becomes evident can contribute to an improved understanding of disease pathogenesis and treatment. A decrease in amyloid-β (Aβ)42 in cerebrospinal fluid (CSF) is suggested to be a biomarker for Aβ deposition in brain. However, the relevance of CSF Aβ levels prior to deposition is not entirely known. Dogs are similar to man with respect to amyloid-β protein precursor (AβPP)-processing, age-related amyloid plaque deposition, and cognitive dysfunction. In the current study, we evaluated the relation between CSF Aβ42 levels and cognitive performance in young to middle-aged dogs (1.5-7 years old). Additionally, CSF sAβPPα and sAβPPβ were measured to evaluate AβPP processing, and CSF cytokines were measured to determine the immune status of the brain. We identified two groups of dogs showing consistently low or high CSF Aβ42 levels. Based on prior studies, it was assumed that at this age no cerebral amyloid plaques were likely to be present. The cognitive performance was evaluated in standard cognition tests. Low or high Aβ concentrations coincided with low or high sAβPPα, sAβPPβ, and CXCL-1 levels, respectively. Dogs with high Aβ concentrations showed significant learning impairments on delayed non-match to position (DNMP), object discrimination, and reversal learning compared to dogs with low Aβ concentrations. Our data support the hypothesis that high levels of CSF Aβ in dogs coincide with lower cognitive performance prior to amyloid deposition. Further experiments are needed to investigate this link, as well as the relevance with respect to Alzheimer's disease pathology progression.
authors.affiliation: Janssen Research & Development, a division of Janssen Pharmaceutica N.V., Beerse, Belgium.
authors.forename: Herman
authors.initials: H
authors.lastname: Borghys
authors.affiliation: Janssen Research & Development, a division of Janssen Pharmaceutica N.V., Beerse, Belgium.
authors.forename: Bianca
authors.initials: B
authors.lastname: Van Broeck
authors.affiliation: Janssen Research & Development, a division of Janssen Pharmaceutica N.V., Beerse, Belgium.
authors.forename: Deborah
authors.initials: D
authors.lastname: Dhuyvetter
authors.affiliation: Janssen Research & Development, a division of Janssen Pharmaceutica N.V., Beerse, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Jacobs
authors.affiliation: Janssen Research & Development, a division of Janssen Pharmaceutica N.V., Beerse, Belgium.
authors.forename: Katja
authors.initials: K
authors.lastname: de Waepenaert
authors.affiliation: Janssen Research & Development, a division of Janssen Pharmaceutica N.V., Beerse, Belgium.
authors.forename: Tim
authors.initials: T
authors.lastname: Erkens
authors.affiliation: Vivocore Inc, Toronto, Canada.
authors.forename: Melissa
authors.initials: M
authors.lastname: Brooks
authors.affiliation: InterVivo Solutions Inc., Toronto, Canada.
authors.forename: Sandy
authors.initials: S
authors.lastname: Thevarkunnel
authors.affiliation: InterVivo Solutions Inc., Toronto, Canada.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Araujo
mesh_terms: D000375:Aging / Q000134:cerebrospinal fluid* / Q000523:psychology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid*; D000818:Animals; D015415:Biomarkers / Q000134:cerebrospinal fluid; D054360:Chemokine CXCL1 / Q000134:cerebrospinal fluid; D002755:Choice Behavior; D003071:Cognition; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid*; D004192:Discrimination, Psychological; D004283:Dog Diseases / Q000134:cerebrospinal fluid*; D004285:Dogs; D005260:Female; D008297:Male; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D012193:Reversal Learning; D012201:Reward
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D054360:Chemokine CXCL1; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer’s disease; amyloid-β peptides; biomarker; cognition; dog