Reduced fibrillar β-amyloid in subcortical structures in a butyrylcholinesterase-knockout Alzheimer disease mouse model

The serine hydrolase, butyrylcholinesterase (BChE) is known to have a variety of enzymatic and nonenzymatic functions. In the brain, BChE is expressed mainly in glia, white matter and in distinct populations of neurons in areas important in cognition. In Alzheimer's disease (AD), many beta-amyloid (Ab) plaques become associated with BChE activity, the significance of which is unclear. A mouse model of AD containing five familial AD genes (5XFAD) also exhibits Ab plaques associated with BChE. We developed a comparable strain (5XFAD/BChE-KO) that is unable to synthesize BChE and reported diminished fibrillar Ab deposits in the cerebral cortex of 5XFAD/BChE-KO mice, compared to 5XFAD counterparts at the same age. This effect was most significant in male mice. The present study extends comparison of the two strains with a detailed examination of fibrillar Ab plaque burden in other regions of the brain that typically accumulate pathology and exhibit neurodegeneration. This work demonstrates that, as in the cerebral cortex, the absence of BChE leads to diminished fibrillar Ab deposition in amygdala, hippocampal formation, thalamus and basal ganglia. This reduction is statistically significant in males, with a trend towards such reduction in female mice. (C) 2016 Published by Elsevier Ireland Ltd.