Amyloid (A) β₄₂ is a protein known to form neuronal plaques - a major factor in the development of Alzheimer’s Disease. Clinical and epidemiological studies have suggested a role for the cytotoxic isoform Aβ₄₂ in type 2 diabetes, and diabetic patients have higher circulating Aβ₄₂. We investigated which peripheral tissues release Aβ₄₂ and found that skeletal muscle and fat release the greatest amount of Aβ_42. To examine the functional consequences of elevated circulating Aβ₄₂ in diabetic mice, we analysed the expression of Amyloid β binding alcohol dehydrogenase (ABAD), a mitochondrial acyl-CoA dehydrogenase that is directly bound and inactivated by Aβ₄₂. Inactivation of ABAD by Aβ₄₂ increases ABAD expression, which was significantly increased in soleus and extensor digitorum longus muscle of db/db mice compared with control tissue (p ≤ 0.05). We next analysed the effect of exogenous Aβ₄₂ administration on metabolic homeostasis in mice. Two weeks of Aβ₄₂ administration (1μg/day) had no effect on glucose and insulin tolerance, but did not result in Aβ₄₂ accumulation in any of the peripheral tissues examined. These data show that Aβ₄₂ is released by peripheral tissues and that increases in peripheral ABAD could be indicative of Aβ₄₂ signalling in these tissues. Studies are currently underway to further investigate the role of Aβ₄₂ ablation in peripheral metabolism.