Differential CSF butyrylcholinesterase levels in Alzheimer's disease patients with the ApoE ε4 allele, in relation to cognitive function and cerebral glucose metabolism

Butyrylcholinesterase (BuChE) is increased in the cerebral cortex of Alzheimer's disease (AD) patients, particularly those carrying A allele of the apolipoprotein E gene (ApoE) and certain BuChE variants that predict increased AD risk and poor response to anticholinesterase therapy. We measured BuChE activity and protein level in CSF of eighty mild AD patients in relation to age, gender, ApoE A genotype, cognition and cerebral glucose metabolism (CMRglc). BuChE activity was 23% higher in men than women (p < 0.03) and 40-60% higher in ApoE A negative patients than in those carrying one or two A alleles (p < 0.0004). CSF BuChE level correlated with cortical CNIRgle. Patients with high to moderate CSF BuChE showed better cognitive function scores than others. We hypothesize that CSF BuChE varies inversely with BuChE in cortical amyloid plaques. Thus, low BuChE in a patient's CSF may predict extensive incorporation in neuritic plaques, increased neurotoxicity and greater central neurodegeneration. (c) 2006 Elsevier Inc. All rights reserved.