Association of Pancreatic Polypeptide with Mild Cognitive Impairment Varies by APOE ε4 Allele

Abstract

We conducted a preliminary case–control investigation of the association of pancreatic polypeptide (PP) with mild cognitive impairment (MCI) in 202 MCI cases (mean age, 81.6 years) and 202 age- and sex-matched cognitively normal controls in the Mayo Clinic Study of Aging. Plasma PP was measured and examined as the natural logarithm (continuous) and dichotomized at the median. The OR (95% CI) of MCI increased with increasing PP [1.46 (1.04–2.05)]. There was a negative interaction of PP with apolipoprotein E (APOE) ε4 allele; compared to the reference group (no APOE ε4 allele and low PP), the OR (95% CI) for combinations of ε4 and PP were: 2.64 (1.39–5.04) for APOE ε4 plus low PP; 2.09 (1.27–3.45) for no APOE ε4 plus high PP; and 1.91 (1.04–3.53) for no APOE ε4 plus high PP (P for interaction = 0.017). There was also a trend toward a negative interaction with type 2 diabetes (P for interaction = 0.058). Compared to no diabetes and low PP, the OR (95% CI) was 3.02 (1.22–7.46) for low PP plus diabetes but 1.80 (1.01–3.22) for high PP plus diabetes. Participants with high PP had a greater mean (SD) weight loss (kilograms per decade) than persons with low PP [−2.27 (4.07) vs. −1.61 (5.24); P = 0.016]. MCI cases had a non-significantly greater weight loss per decade compared to controls. These findings suggest that high PP alone or jointly with APOE ε4 allele or type 2 diabetes is associated with MCI, and that high PP may mitigate some effects of APOE ε4 allele and type 2 diabetes on cognition. Potential mechanisms may involve PP-related weight loss and centrally mediated effects of PP on cognition. These findings remain to be validated in other studies.

Blood-based protein mediators of senility with replications across biofluids and cohorts

“…PPP levels rise exponentially with age ( Brimnes et al., 1997) and are associated with anorexia and weight loss in older persons ( Moss et al , 2012 ). High plasma PPP levels are associated with both weight loss and MCI and moderate the association of diabetes with that diagnosis ( Roberts et al , 2015 ).…”

Using redescription mining to relate clinical and biological characteristics of cognitively impaired and Alzheimer’s disease patients

“…Finally, we also found alteration in plasma levels of several other attributes, whose relationship with AD has already been shown in the literature. These include increase in serum apolipoprotein B (APOB) [69], pancreatic polypeptide (PPP) [70,71] and for very small groups, the increase of plasma insulin [72] and the CSF macrophage migration inhibitory factor (MCRPHMIF) [73] in AD brain. Fas (CD95) ligand (FASL) levels are found to be significantly decreased in LMCI patients compared to AD and CN subjects in our dataset.…”