Affiliations: [a] Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA | [b] Eppley Institute, University of Nebraska Medical Center, Omaha, NE, USA | [c] Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, USA
Correspondence:
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Corresponding authors: Dr. Patricio F. Reyes, Alzheimer's Disease and Cognitive Disorders Clinic, Barrow Neurological Institute St. Joseph's Hospital and Medical Center 500 West Thomas Road, Suite 720, Phoenix, AZ 85013, USA. Tel.: +1 602 406 4784; Fax: +1 602 798 9504; E-mail: [email protected]; Dr. Debomoy K. Lahiri, Department of Psychiatry, Indiana University School of Medicine, 791 Union Drive, Indianapolis, IN 46202-4887, USA. Tel.: +1 317 274 2706; Fax: +1 317 274 1365; E-mail: [email protected]
Abstract: The ‘cholinergic hypothesis’, based on the correlation of the reduction of cholinergic activity in Alzheimer's disease (AD) with cognition and memory, is currently the most widely-held view for AD. Drug treatments for AD focus mainly on inhibition of acetylcholinesterase (AChE), and to some extent butyrylcholinesterase (BChE). In addition to changes in AChE in AD, there is a rise in the level of the sister enzyme BChE. However, the role of the two cholinesterases is poorly understood in vivo. We characterized several proteins immunohistochemically in brain sections from AChE nullizygote (AChE−/−) and wild type AChE+/+ mice. Previous studies had shown that AChE−/− mouse tissues are devoid of AChE activity and that the overall cholinesterase activity is significantly decreased in the knockout group [16]. Despite the differences of cholinesterase activity, we found no significant structural alterations between the experimental groups. Immunohistochemical examination revealed no neuronal, dendritic, astrocytic, synaptic, microglial, and endothelial differences between AChE−/− and AChE+/+ mice. Similarly, the histochemical examination showed no morphologic alterations between AChE−/− and AChE+/+ mice. Our studies show that neither the absence of AChE nor the presence exclusively of BChE is associated with neuroglial and vascular pathology.
