Plasma Amyloid Beta Concentrations in Aged and Cognitively Impaired Pet Dogs.

ABSTRACT

Longevity-associated neurological disorders have been observed across human and canine aging populations. Alzheimer's disease (AD) and canine cognitive dysfunction syndrome (CDS) represent comparable diseases affecting both species as they age. Translational diagnostic and therapeutic research is needed for these incurable diseases. The amyloid ß (Aß) peptide family are AD-associated peptides with identical amino acid sequences between dogs and humans. Plasma Aß42 concentration increases with age and decreases with AD in humans, and cerebrospinal fluid (CSF) concentration decreases in AD and correlates inversely with the amyloid load within the brain. Similarly, CSF Aß42 concentrations decrease in dogs with CDS but there is limited and conflicting information on plasma Aß42 concentrations in aging dogs and dogs with CDS. We measured plasma concentrations of Aß42 and Aß40 with an ultrasensitive single-molecule array assay (SIMOA) in a population of healthy aging dogs of different life stages (n = 36) and dogs affected with CDS (n = 11). In addition, the ratio of Aß42/ß40 was calculated. The mean plasma concentrations of Aß42 and Aß40 increased significantly with age (r2 = 0.27, p = 0.001; and r2 = 0.42, p < 0.001, respectively) and with life stage puppy/junior group (0.43-2 years) 1.23 ± 0.95 and 38.26 ± 49.43 pg/mL; adult/mature group (2.1-9 years) 10.99 ± 5.45 and 131.05 ± 80.17 pg/mL; geriatric/senior group (9.3-14.5 years) 18.65 ± 16.65 and 192.88 ± 146.38 pg/mL, respectively. Concentrations of Aß42 and Aß40 in dogs with CDS (11.0-15.6 years) were significantly lower than age-matched healthy dogs at 11.61 ± 6.39 and 150.23 ± 98.2 pg/mL (p = 0.0048 and p = 0.001), respectively. Our findings suggest the dynamics of canine plasma amyloid concentrations are analogous to that found in aging humans with and without AD.