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The apolipoprotein E ε4 allele plays pathological roles in AD through high protein expression and interaction with butyrylcholinesterase.

Abstract：

:The apolipoprotein E (ApoE) ε4 allele has consistently been established as an Alzheimer's disease (AD) risk factor, but its pathological contribution to AD is obscure. Certain butyrylcholinesterase (BuChE) polymorphisms together with the ApoE ε4 allele synergistically increase the risk of AD. In addition, AD risk factors, i.e. advanced age, female gender and ApoE ε4 are associated with different levels of CSF BuChE in AD patients, and BuChE protein attenuates Aβ fibrillization in vitro. Here we investigated the roles of ApoE and BuChE gene products as modulators of pathological features of AD in vivo. We found that AD risk factors were associated with different levels of ApoE protein in the CSF of AD patients (n=115). Women and ApoE ε4 carriers had the highest levels of ApoE protein (up by 50-120%, p<0.01-0.0001), which were increased with age (r=0.30, p<0.0006). The CSF surrogate markers of pathological features of AD, i.e. high tau and P-tau, low Aβ(42) and high tau/Aβ(42) ratio, were associated with high levels of ApoE protein. Intriguingly, high ApoE protein levels were not only associated with low amounts of BuChE, but they also altered the aging and activity of this enzyme in concentration- and isoform-dependent manners, particularly in the presence of Aβ peptides. Both ApoE and BuChE levels were also differentially related to levels of the proinflammatory cytokine IL-1β. In conclusion, ApoE ε4 might impart its pathological role through high protein expression and interaction with BuChE, which in turn might modulate central cholinergic activity and Aβ load in the brain.

journal_name

Neurobiol Aging

journal_title

Neurobiology of aging

authors

Darreh-Shori T,Modiri N,Blennow K,Baza S,Kamil C,Ahmed H,Andreasen N,Nordberg A

doi

10.1016/j.neurobiolaging.2009.07.015

subject

Has Abstract

pub_date

2011-07-01 00:00:00

pages

1236-48

issue

7

eissn

0197-4580

issn

1558-1497

pii

S0197-4580(09)00246-2

journal_volume

32

pub_type

杂志文章

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