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Total apolipoprotein E levels and specific isoform composition in cerebrospinal fluid and plasma from Alzheimer's disease patients and controls

Martinez-Morillo, Eduardo; Hansson, Oskar LU ; Atagi, Yuka; Bu, Guojun; Minthon, Lennart LU ; Diamandis, Eleftherios P. and Nielsen, Henrietta LU (2014) In Acta Neuropathologica 127(5). p.633-643
Abstract
The apolipoprotein E (ApoE) epsilon 4 allele is the strongest risk factor of sporadic Alzheimer's disease (AD), however, the fluid concentrations of ApoE and its different isoforms (ApoE2, ApoE3 and ApoE4) in AD patients and among APOE genotypes (APOE epsilon 2, epsilon 3, epsilon 4) remain controversial. Using a novel mass spectrometry-based method, we quantified total ApoE and specific ApoE isoform concentrations and potential associations with age, cognitive status, cholesterol levels and established AD biomarkers in cerebrospinal fluid (CSF) from AD patients versus non-AD individuals with different APOE genotypes. We also investigated plasma total ApoE and ApoE isoform composition in a subset of these individuals. In total n = 43 AD... (More)
The apolipoprotein E (ApoE) epsilon 4 allele is the strongest risk factor of sporadic Alzheimer's disease (AD), however, the fluid concentrations of ApoE and its different isoforms (ApoE2, ApoE3 and ApoE4) in AD patients and among APOE genotypes (APOE epsilon 2, epsilon 3, epsilon 4) remain controversial. Using a novel mass spectrometry-based method, we quantified total ApoE and specific ApoE isoform concentrations and potential associations with age, cognitive status, cholesterol levels and established AD biomarkers in cerebrospinal fluid (CSF) from AD patients versus non-AD individuals with different APOE genotypes. We also investigated plasma total ApoE and ApoE isoform composition in a subset of these individuals. In total n = 43 AD and n = 43 non-AD subjects were included. We found that CSF and plasma total ApoE levels did not correlate with age or cognitive status and did not differ between AD and non-AD subjects deeming ApoE as an unfit diagnostic marker for AD. Also, whereas CSF ApoE levels did not vary between APOE genotypes APOE epsilon 4 carriers exhibited significantly decreased plasma ApoE levels attributed to a specific decrease in the ApoE4 isoform concentrations. CSF total ApoE concentrations were positively associated with CSF, total tau, tau phosphorylated at Thr181 and A beta 1-42 of which the latter association was weaker and only present in APOE epsilon 4 carriers indicating a differential involvement of ApoE in tau versus A beta-linked neuropathological processes. Future studies need to elucidate whether the observed plasma ApoE4 deficiency is a life-long condition in APOE E > 4 carriers and whether this decrease in plasma ApoE predisposes APOE E > 4 carriers to AD. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Apolipoprotein E, Cerebrospinal fluid, Isoform, Mass spectrometry, Plasma
in
Acta Neuropathologica
volume
127
issue
5
pages
633 - 643
publisher
Springer
external identifiers
  • wos:000334426300002
  • scopus:84899898187
ISSN
1432-0533
DOI
10.1007/s00401-014-1266-2
language
English
LU publication?
yes
id
2727d4e3-0f1f-4dd9-b217-ad6d934e338c (old id 4487905)
date added to LUP
2014-07-01 07:33:41
date last changed
2017-09-10 03:55:49
@article{2727d4e3-0f1f-4dd9-b217-ad6d934e338c,
  abstract     = {The apolipoprotein E (ApoE) epsilon 4 allele is the strongest risk factor of sporadic Alzheimer's disease (AD), however, the fluid concentrations of ApoE and its different isoforms (ApoE2, ApoE3 and ApoE4) in AD patients and among APOE genotypes (APOE epsilon 2, epsilon 3, epsilon 4) remain controversial. Using a novel mass spectrometry-based method, we quantified total ApoE and specific ApoE isoform concentrations and potential associations with age, cognitive status, cholesterol levels and established AD biomarkers in cerebrospinal fluid (CSF) from AD patients versus non-AD individuals with different APOE genotypes. We also investigated plasma total ApoE and ApoE isoform composition in a subset of these individuals. In total n = 43 AD and n = 43 non-AD subjects were included. We found that CSF and plasma total ApoE levels did not correlate with age or cognitive status and did not differ between AD and non-AD subjects deeming ApoE as an unfit diagnostic marker for AD. Also, whereas CSF ApoE levels did not vary between APOE genotypes APOE epsilon 4 carriers exhibited significantly decreased plasma ApoE levels attributed to a specific decrease in the ApoE4 isoform concentrations. CSF total ApoE concentrations were positively associated with CSF, total tau, tau phosphorylated at Thr181 and A beta 1-42 of which the latter association was weaker and only present in APOE epsilon 4 carriers indicating a differential involvement of ApoE in tau versus A beta-linked neuropathological processes. Future studies need to elucidate whether the observed plasma ApoE4 deficiency is a life-long condition in APOE E > 4 carriers and whether this decrease in plasma ApoE predisposes APOE E > 4 carriers to AD.},
  author       = {Martinez-Morillo, Eduardo and Hansson, Oskar and Atagi, Yuka and Bu, Guojun and Minthon, Lennart and Diamandis, Eleftherios P. and Nielsen, Henrietta},
  issn         = {1432-0533},
  keyword      = {Apolipoprotein E,Cerebrospinal fluid,Isoform,Mass spectrometry,Plasma},
  language     = {eng},
  number       = {5},
  pages        = {633--643},
  publisher    = {Springer},
  series       = {Acta Neuropathologica},
  title        = {Total apolipoprotein E levels and specific isoform composition in cerebrospinal fluid and plasma from Alzheimer's disease patients and controls},
  url          = {http://dx.doi.org/10.1007/s00401-014-1266-2},
  volume       = {127},
  year         = {2014},
}