Association of butyrylcholinesterase K variant with cholinesterase-positive neuritic plaques in the temporal cortex in late-onset Alzheimer's disease

Abstract

In confirmed late-onset (>65 years) Alzheimer's disease, we found a greater load, both of overall neuritic plaques and of cholinesterase-positive neuritic plaques, in the temporal cortex of carriers of the butyrylcholinesterase K variant (BCHE-K) aged <80 years than of all other patients. The differences were most striking in the case of cholinesterase-positive neuritic plaques. Among BCHE-K carriers, densities of such plaques were over six times higher in patients <80 years at death than in those >80 years (P=0.01). Furthermore, in subjects <80 years, BCHE-K carriers had nearly six-fold greater densities of these plaques than non-carriers (P=0.009). We consider three potential explanations for these findings: that the K variant binds more readily to plaque constituents, that it promotes fibril formation or that it induces aberrant neurite growth.

Candidate gene association studies of genes involved in neuronal cholinergic transmission in Alzheimer's disease suggests choline acetyltransferase as a candidate deserving further study

“…The genotype and allele frequencies of the control samples were comparable to those reported in the literature [Lehmann et al, 2001;Mubumbila et al, 2002]. It has been suggested that the failure to replicate the significance of the K-variant, or indeed other putative risk genes, could be attributed to sampling variables for each cohort studied [Lehmann et al, 2000[Lehmann et al, , 2001. A justifiable concern regards the diagnostic criteria, as the majority of K-variant ''positive'' studies had used necropsy-confirmed cases.…”

Association of BDNF and BCHE with Alzheimer's disease: Meta-analysis based on 56 genetic case-control studies of 12,563 cases and 12,622 controls

“…Additionally, the BCHE-K variant promotes fibril formation by participating in the transformation of Aβ from an initially benign form to an eventually malignant form. The BCHE-K variant acts as a general candidate risk factor of AD (84,85). Six significant results (46-51) and 22 non-significant results (5, were found in previous studies on the association between the BCHE-K variant and AD.…”

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

“…Investigations of this BCHE variant have observed that its presence pre-empts progression of AD (Sandbrink et al, 1998;O'Brien et al, 2003). However, other studies have suggested that this variant is associated with AD (Tilley et al, 1999;Wiebusch et al, 1999;Lehmann et al, 2000;Lehmann et al, 2001;McIlroy et al, 2000) and still others have observed no association of BCHE-K variant with AD (Hiltunen et al, 1998;Kehoe et al, 1998;Singleton et al, 1998;Grubber et al, 1999;Ki et al, 1999;Yamamoto et al, 1999). This suggests that the role(s) of BChE in AD may involve other components of the disease and requires further scrutiny.…”