Abstract
Accumulation of the 42 aa amyloid b protein (Ab42) is a defining feature of Alzheimer’s disease (AD). A 1.5 fold increase in Ab precursor (APP) expression is sufficient to cause familial AD (FAD). We hypothesize that the post-prandial increase in limiting nutrients – aa and glucose – will transiently stimulate protein synthesis and by extension APP. Our interprofessional team determined the post-prandial APP and Ab42 changes in plasma of 20 fasting healthy older adults with a normal Mini-cog and without metabolic disorders after consuming a protein-rich beverage. A Comprehensive Metabolic Panel analysis demonstrated that total plasma protein, glucose and liver function markers were not increased 2h after the meal. APP levels increased significantly starting at 1h (p=0.024 for difference to 4h). Fasting APP measures were compromised by dehydration-induced platelet lysis. Post-prandial Ab42 levels increased with a peak at 2 h (p=0.004) and dropped at subsequent time points. In agreement with literature, fasting Ab42 levels trended to reduce in subjects with a family history of AD/dementia. Subjects with a family history of AD/dementia showed a larger increase in Ab, but the levels also dropped more rapidly, a phenomenon that needs to be systematically evaluated. These data suggest that periodic postprandial increases in APP that saturate the turnover pathways may facilitate the accumulation of Ab associated with AD pathology. Systematic analysis of diets that limit such increases may be useful in prevention of age-related dementia and other proteinopathies.