Chunk #18 — Introduction — Rationale for the present study: Mechanisms of Alzheimer’s disease identified as upstream regulators of alcohol-sensitive protein networks in C57BL/6J mice
Predictably, many of the alcohol-sensitive proteins are abnormally expressed in the brains of AD patients. Indeed, proteomic studies of CSF/plasma from human Alzheimer’s patients (Robinson, Amin, & Guest, 2017) and transgenic mouse models of AD (Chang, Nouwens, Dodd, & Etheridge, 2013; Fu et al., 2015; Takano et al., 2013) show considerable overlap between AD-linked protein networks and the alcohol-sensitive networks shown here. Notably, heat shock proteins and creatinine kinases were upregulated and total levels of DPYSL2 (CRMP2) a microtubule protein, was decreased in the proteomics study but is consistently hyperphosphorylated in postmortem human brains and transgenic lines. This is a consistent, yet curious, finding because heat shock proteins are thought to protect the brain from increasing amounts of oxidative stress and toxicity due to accumulated Aβ aggregates (Rivera, Capone, Cauvi, Arispe, & De Maio, 2018). It is possible that HSPs are increasing in a compensatory fashion in response to both the detrimental consequences of alcohol and of increasing levels of AB in the brain. Likewise, total levels of CRMP2 may be blunted in the alcohol-drinking mice because more of the
