Association of periodontal disease with breed size, breed, weight, and age in pure-bred client-owned dogs in the United States.

Despite periodontal disease (PD) being amongst the most common diagnoses in primary-care practice, the disease is generally underdiagnosed. However, the millions of clinical records generated by pet hospitals each year provide unique opportunities to generate insights about disease risk across large numbers of dogs. The objective of this study was to undertake a retrospective analysis of medical records to ascertain which sizes and breeds of dog are most frequently diagnosed with PD. Although data collection regarding PD was not consistent, it was assumed that the same inconsistencies in recording periodontal abnormalities were present across the range of bodyweight, breed categories and breeds. Over 3 million medical records across 60 breeds of dogs visiting a chain of veterinary hospitals in the United States collected over a 5-year period were analysed. Statistical analysis of a subset of these records found that extra-small (<6.5 kg) breeds of dog were up to five times more likely to be diagnosed with PD than giant breeds (>25 kg) (P <0.0001). The majority of breeds most frequently diagnosed with PD were in the extra-small, small (6.5-9 kg) and medium-small (9-15 kg) breed size categories. Additional risk factors for PD diagnosis included age, being overweight and time since last scale and polish. Veterinarians should consider targeting client education about dental health, and diagnostic efforts, towards canine patients of the small-breed size categories and those with a higher risk of developing PD (e.g. overweight).

Decreased parkin solubility is associated with impairment of autophagy in the nigrostriatum of sporadic Parkinson's disease.

Parkinson's disease (PD) is a motor disorder that involves death of dopaminergic neurons in the substantia nigra pars compacta. Parkin is an autosomal recessive gene that is mutated in early onset PD. We investigated the role of parkin and autophagic clearance in postmortem nigrostriatal tissues from 22 non-familial sporadic PD patients and 15 control samples. Parkin was insoluble with altered cytosolic expression in the nigrostriatum of sporadic PD. Parkin insolubility was associated with lack of degradation of ubiquitinated proteins and accumulation of α-Synuclein and parkin in autophagosomes, suggesting autophagic defects in PD. To test parkin's role in mediating autophagic clearance, we used lentiviral gene transfer to express human wild type or mutant parkin (T240R) with α-Synuclein in the rat striatum. Lentiviral expression of α-Synuclein led to accumulation of autophagic vacuoles, while co-expression of parkin with α-Synuclein facilitated autophagic clearance. Subcellular fractionation showed accumulation of α-Synuclein and tau hyper-phosphorylation (p-Tau) in autophagosomes in gene transfer models, similar to the effects observed in PD brains, but parkin expression led to protein deposition into lysosomes. However, parkin loss of function mutation did not affect autophagic clearance. Taken together, these data suggest that functional parkin regulates autophagosome clearance, while decreased parkin solubility may alter normal autophagy in sporadic PD.