ACHE and Alzheimer disease: In AD, the two main microscopic hallmarks of disease, the abnormal accumulation of extracellular protein material in the amyloid–beta plaques and the formation of intracellular neurofibrillary tangles, are associated with abnormal expression of acetylcholinesterase (AChE), which leads to decreased levels of neurotransmitter acetylcholine (ACh), synaptic alteration, and impaired memory and learning [152].