A striking commonality of the alcohol-sensitive proteins that were upregulated in the mPFC and AMY is their notable relevance to AD pathology. Creatine kinase B (CKB), hexokinase (HK1), syntaxin binding protein 1 (STXB1/MUNC-18), amphiphysin (AMPH), complexin, and heat shock proteins are all upregulated in the cortex of AD patients and in normal, alcohol-drinking C57BL/6J mice (Donovan et al., 2012; Jacobs, Williams, & Francis, 2006; Lynn, Wang, Markesbery, & Lovell, 2010; Rivera et al., 2018). Further, CKB and HK1 are more prominently increased in the brains of individuals with early- vs late-stage disease suggesting that proteins relevant for energy use and metabolism may be early markers of brain pathology and stress. Munc-18 and complexin are part of a family of neuronal vesicular proteins regulating the SNARE complex which is involved in rapid exocytosis and neurotransmitter release at neuronal synapses (Pabst et al., 2002; Sudhof, 2013; Tang et al., 2006). Mechanistically, this complex directly binds to APP causing increased aggregation of Aβ in the brain and indeed, these proteins are physically located in proximity to aggregated Aβ (Chaufty, Sullivan, & Ho, 2012; Jensen, Albertsen, Bartling, Haugaard-Kedstrom, & Stromgaard, 2018).
