MMP2 and Cognitive impairment: These changes included loss of microtubule-associated protein-2 in CA1 [120], reduced hippocampal cytochrome oxidase [121], impaired monoamine neurotransmitter turnover [108], altered glucose utilization [122], reduced post-synaptic cholinergic activity [123], increased heme oxygenase [124] and matrix metalloproteinase (MMP)-2 expression [125], and reactive gliosis, leading to a state of impaired energy metabolism, disturbed protein synthesis, and increased oxidative stress, which were detectable months prior to the onset of hippocampal neuronal loss or cognitive impairment.