Butyrylcholinesterase-knockout reduces brain deposition of fibrillar β-amyloid in an Alzheimer mouse model

Abstract

In Alzheimer's disease (AD), numerous β-amyloid (Aβ) plaques are associated with butyrylcholinesterase (BChE) activity, the significance of which is unclear. A mouse model, containing five human familial AD genes (5XFAD), also develops Aβ plaques with BChE activity. Knock-out of BChE in this model showed diminished fibrillar Aβ plaque deposition, more so in males than females. This suggests that lack of BChE reduces deposition of fibrillar Aβ in AD and this effect may be influenced by sex.

Complexity across scales: a walkthrough to linking neuro-imaging readouts to molecular processes

“…This complex alters the structure of BCHE which accelerates the catalytic activity of the enzyme. This results in the formation of amyloid plaques [168][169][170] as seen Figure 5. Increased expression of APOE also disrupts the neuronal activity in the hippocampus resulting in atrophy.…”

The diabetic brain and cognition

“…Whereas brain hyperglycemia mediates hippocampal neuron responses (Macauley et al 2015), BCHE levels also correlate with cerebral glucose metabolism and cerebral Ab load (Darreh-Shori et al 2011). BChE associates particularly with the malignant form of Ab plaques, suggesting its role in transforming non-fibrillar to the malignant fibrillar form (Reid and Darvesh 2015). To account for a gender difference, a genegene interaction between BChE and estrogen-associated genes was proposed (Reid and Darvesh 2015).…”

“…BChE associates particularly with the malignant form of Ab plaques, suggesting its role in transforming non-fibrillar to the malignant fibrillar form (Reid and Darvesh 2015). To account for a gender difference, a genegene interaction between BChE and estrogen-associated genes was proposed (Reid and Darvesh 2015). However, the relation between BChE and AD is not settled yet.…”

Synthesis and Preliminary Evaluation of Phenyl 4-123I-Iodophenylcarbamate for Visualization of Cholinesterases Associated with Alzheimer Disease Pathology

“…Brain tissue sections adjacent to those used for autoradiography were stained and analyzed for cholinesterases and thioflavin-S using previously described methods (14,17).…”

“…Additionally, these enzymes associate with Ab plaques and neurofibrillary tangles in AD (14,15). The significance of this association remains unclear but may be related to Ab plaque formation and maturation (16,17). In addition, cholinesterases may associate predominantly with AD plaques and not those found in cognitively normal brain (16,18,19).…”