Shen_2004_Med.Hypotheses_63_285

Substantial evidence is presented demonstrating that it is the cholinesterases (ChEs) that constitute the organizer, the connector and the safeguard for multiple neurochemical functions and mature anatomical architecture of the brain. In Alzheimer's disease (AD), the histopathological characteristics are initially and primarily associated with the degeneration of the acetylcholinesterase (AChE) system in various brain regions. Multiple classic and/or putative neurotransmitters and neuromodulators, virtually all the peptide hormones of the endocrine and neuroendocrine systems in the brain, their specific synthesizing and hydrolyzing marker enzymes and associated uptake processes (transporters), and receptors, do not actually participate in the formation of senile plaques and neurofibrillary tangles in the brains of patients suffering from AD. The massive perturbation in different neurochemicals seen in AD is essentially caused by the ChEs-associated pathology. The graded patterns of brain ChEs expression affect the preferential vulnerability and severity of the AD clinico-pathologic presentation. It seems that the common law in nature may also dominate the destiny of brain ChEs system, i.e., the weaker the cells express AChE, the more susceptible the cells are to AD degeneration, and vice versa.