Chunk #16 — Introduction — Rationale for the present study: Mechanisms of Alzheimer’s disease identified as upstream regulators of alcohol-sensitive protein networks in C57BL/6J mice
Here, we reanalyzed fold-change data (alcohol intake vs control) from the alcohol-sensitive protein networks (Agoglia & Hodge, 2017; Salling et al., 2016) using Ingenuity Pathway Analysis (IPA) Upstream Regulator Analysis (URA) to elucidate potential upstream regulatory molecules that may explain observed changes in protein networks (Kramer, Green, Pollard, & Tugendreich, 2014). In the PFC and AMY datasets, the URA identified MAPT (Tau), APP (amyloid precursor protein), and PSEN-1 (presenilin-1) as the most probable upstream modulators of alcohol-sensitive protein networks (Fig. 1C). In the PFC, 12 Alzheimer’s-associated proteins were identified as downstream targets of Tau, APP, and PSEN-1 (Fig. 1D, left). Similarly, 11 Alzheimer’s-associated proteins were identified in the AMY as downstream targets of Tau, APP, and PSEN-1 (Fig. 1D, right). These findings indicate that alcohol intake influences protein networks that are downstream of primary molecular determinants of AD, which suggests that alcohol may influence risk of AD-related pathology in the PFC and AMY.
