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. Here, MAP2 is linked to Cognitive impairment.