In VDAC1+/+, (i) dissociation of hexokinase (HK) results in a “closed” VDAC configuration that prevents adenine nucleotide exchange and uncouples intra and extramitochondrial metabolism, (ii) shifts the equilibrium to the VDAC1 oligomeric state, mediating the release of apoptogenic proteins and leading to apoptosis, (iii) Elevated GSK3β activity is a key event in phosphorylation of Tau and synaptic pathology in AD. Here, HK1 is linked to Alzheimer disease.