Metabolic syndrome exacerbates amyloid pathology in a comorbid Alzheimer's mouse model.

Alzheimer's disease (AD) often coexists with other aging-associated diseases including obesity, diabetes, hypertension, and cardiovascular diseases. The early stage of these comorbidities is known as metabolic syndrome (MetS) which is highly prevalent in mid-life. An important cause of MetS is the deficiency of SIRT3, a mitochondrial deacetylase which enhances the functions of critical mitochondrial proteins, including metabolic enzymes, by deacetylation. Deletion of Sirt3 gene has been reported to result in the acceleration of MetS. In a recently published study, we demonstrated in the brain of Sirt3-/- mice, downregulation of metabolic enzymes, insulin resistance and elevation of inflammatory markers including microglial proliferation. These findings suggested a novel pathway that could link SIRT3 deficiency to neuroinflammation, an important cause of Alzheimer's pathogenesis. Therefore, we hypothesized that MetS and amyloid pathology may interact through converging pathways of insulin resistance and neuroinflammation in comorbid AD. To investigate these interactions, we crossed Sirt3-/- mice with APP/PS1 mice and successfully generated APP/PS1/Sirt3-/- mice with amyloid pathology and MetS. In these comorbid AD mice, we observed exacerbation of insulin resistance, glucose intolerance, amyloid plaque deposition, markers of neuroinflammation, including elevated expression of IL-1ß, TNF-α and Cox-2 at 8 months of age. There was also increased microglial proliferation and activation. Our observations suggest a novel mechanism by which MetS may interact with amyloid pathology during the cellular phase of AD. Therapeutic targeting of SIRT3 in AD with comorbidities may produce beneficial effects.

Postoperative glaucoma in the Labrador Retriever: incidence, risk factors, and visual outcome following routine phacoemulsification.

OBJECTIVE: To evaluate the incidence and risk factors associated with development of postoperative glaucoma in the Labrador Retriever following routine phacoemulsification. METHODS: Medical records from Labradors and a randomly selected population of non-Labradors were retrospectively evaluated. Signalment, diabetic status, cataract stage, gonioscopic findings, presence of preoperative lens-induced uveitis, development of postoperative hypertension (POH), postoperative glaucoma and postoperative visual status were recorded for each patient. Survival curves were developed using the Cox proportional hazards model. RESULTS: Forty-two Labradors (66 eyes) and 199 non-Labradors (314 eyes) were included. The incidence of POH was significantly higher in Labradors (33%) than non-Labradors (18%). Labradors were at significantly increased risk of postoperative glaucoma and blindness compared to non-Labradors. Estimated probabilities of postoperative glaucoma in Labradors were 23%, 25%, 30% and 35% at weeks 4, 26, 52 and 104, respectively, compared with 5%, 6%, 7% and 9% at weeks 4, 26, 52 and 104, respectively, in non-Labradors. Estimated probabilities of postoperative blindness in Labradors were 5%, 9%, 15% and 27% at weeks 4, 26, 52 and 104, respectively, compared with 2%, 3%, 5% and 10% at weeks 4, 26, 52 and 104, respectively, in non-Labradors. Risk factors for the development of glaucoma in Labradors included increasing age and development of POH. No statistically significant risk factors for the development of glaucoma were identified in non-Labradors. CONCLUSIONS: Labradors are at increased risk of glaucoma and blindness following phacoemulsification compared with non-Labradors. POH and increasing age represent risk factors for the development of postoperative glaucoma in Labradors.