Darreh-Shori_2011_Neurobiol.Aging_32_2320 e15

Reference

Title : Differential levels of apolipoprotein E and butyrylcholinesterase show strong association with pathological signs of Alzheimer's disease in the brain in vivo - Darreh-Shori_2011_Neurobiol.Aging_32_2320 e15
Author(s) : Darreh-Shori T , Forsberg A , Modiri N , Andreasen N , Blennow K , Kamil C , Ahmed H , Almkvist O , Langstrom B , Nordberg A
Ref : Neurobiology of Aging , 32 :2320 e15 , 2011
Abstract :

Recently, we reported that 3 of the known risk factors of Alzheimer's disease (AD), i.e., advanced age, apolipoprotein E (ApoE) epsilon4, and female gender, are associated with differential levels of ApoE proteins and butyrylcholinesterase (BuChE) in the cerebrospinal fluid (CSF) of AD patients. The ApoE epsilon4 allele and certain BuChE polymorphisms synergistically affect the conversion rate of mild cognitive impairment (MCI) to AD. Here, we investigated interrelationships between ApoE and BuChE levels, and pathological markers of AD in vivo. CSF from patients with probable AD, assessed for cerebral glucose metabolism (CMRglc; n = 50) and Pittsburgh compound B (PIB) retention (beta-amyloid [Abeta] load, n = 29) by positron emission tomography (PET), was used for measurement of BuChE, ApoE, Abeta, tau, phosphorylated tau (P-tau) and interleukin-1beta (IL-1beta) levels. Levels of ApoE and BuChE strongly correlated with CMRglc (fluorodeoxyglucose [FDG]-PET, r = 0.54, p < 0.0001, n = 50), cerebral Abeta load (PIB retention, r = 0.73, p < 0.0001, n = 29), and CSF P-tau (r = 0.73, p < 0.0001, n = 33). High ApoE protein was tied to low CMRglc and high PIB retention and P-tau. BuChE levels had opposite relationships. Other CSF covariates were levels of interleukin-1beta and Abeta(42) peptide. The pattern of the patients' cognitive Z-scores strongly supported these observations. High ApoE protein was also linked to changes in 3 of the biodynamic properties of BuChE. In vitro analysis indicated that high ApoE protein levels were related to an increased pool of dormant BuChE molecules with an abnormally high intrinsic catalytic rate in CSF, which was "turned on" by excess Abeta peptides. The findings suggest that abnormally high levels of ApoE may play a causative role in the pathological events of AD, particularly those involving the early cholinergic deficit in the AD brain, through modulation of cholinesterases activities, hence disturbing the acetylcholine-dependent activity of neurons and nonexcitable cells such as glial cells.

PubMedSearch : Darreh-Shori_2011_Neurobiol.Aging_32_2320 e15
PubMedID: 20538374

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Citations formats

Darreh-Shori T, Forsberg A, Modiri N, Andreasen N, Blennow K, Kamil C, Ahmed H, Almkvist O, Langstrom B, Nordberg A (2011)
Differential levels of apolipoprotein E and butyrylcholinesterase show strong association with pathological signs of Alzheimer's disease in the brain in vivo
Neurobiology of Aging 32 :2320 e15

Darreh-Shori T, Forsberg A, Modiri N, Andreasen N, Blennow K, Kamil C, Ahmed H, Almkvist O, Langstrom B, Nordberg A (2011)
Neurobiology of Aging 32 :2320 e15