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Acute phase markers in CSF reveal inflammatory changes in Alzheimer's disease that intersect with pathology, APOE ε4, sex and age

Ayton, Scott ; Janelidze, Shorena LU ; Roberts, Blaine ; Palmqvist, Sebastian LU orcid ; Kalinowski, Pawel ; Diouf, Ibrahima ; Belaidi, Abdel A. ; Stomrud, Erik LU orcid ; Bush, Ashley I. and Hansson, Oskar LU orcid (2021) In Progress in Neurobiology 198.
Abstract

It is unknown how neuroinflammation may feature in the etiology of Alzheimer's disease (AD). We profiled acute phase response (APR) proteins (α1-antitrypsin, α1-antichymotrypsin, ceruloplasmin, complement C3, ferritin, α-fibrinogen, β-fibrinogen, γ-fibrinogen, haptoglobin, hemopexin) in CSF of 1291 subjects along the clinical and biomarker spectrum of AD to investigate the association between inflammatory changes, disease outcomes, and demographic variables. Subjects were stratified by Aβ42/t-tau as well as the following clinical diagnoses: cognitively normal (CN); subjective cognitive decline (SCD); mild cognitive impairment (MCI); and AD dementia. In separate multiple regressions (adjusting for diagnosis, age, sex, APOE-ε4)... (More)

It is unknown how neuroinflammation may feature in the etiology of Alzheimer's disease (AD). We profiled acute phase response (APR) proteins (α1-antitrypsin, α1-antichymotrypsin, ceruloplasmin, complement C3, ferritin, α-fibrinogen, β-fibrinogen, γ-fibrinogen, haptoglobin, hemopexin) in CSF of 1291 subjects along the clinical and biomarker spectrum of AD to investigate the association between inflammatory changes, disease outcomes, and demographic variables. Subjects were stratified by Aβ42/t-tau as well as the following clinical diagnoses: cognitively normal (CN); subjective cognitive decline (SCD); mild cognitive impairment (MCI); and AD dementia. In separate multiple regressions (adjusting for diagnosis, age, sex, APOE-ε4) of each APR protein and a composite of all APR proteins, CSF Aβ42/t-tau status was associated with elevated ferritin, but not any other APR protein in CN and SCD subjects. Rather, the APR was elevated along with symptomatic progression (CN < SCD < MCI < AD), and this was elevation was mediated by CSF p-tau181. APOE ε4 status did not affect levels of any APR proteins in CSF, while these were elevated in males and with increased age. The performance of the APR in predicting clinical diagnosis was influenced by APOE ε4 status, sex, and age. These data provide new insight into inflammatory changes in AD and how this intersects with pathology changes and patient demographics.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
acute phase response, Alzheimer's disease, biomarkers, Neuroinflammation
in
Progress in Neurobiology
volume
198
article number
101904
publisher
Elsevier
external identifiers
  • scopus:85090485253
  • pmid:32882319
ISSN
0301-0082
DOI
10.1016/j.pneurobio.2020.101904
language
English
LU publication?
yes
id
dcc3c780-3c53-4b01-af0b-bb2b322ae07e
date added to LUP
2020-10-21 10:11:08
date last changed
2024-06-14 00:25:24
@article{dcc3c780-3c53-4b01-af0b-bb2b322ae07e,
  abstract     = {{<p>It is unknown how neuroinflammation may feature in the etiology of Alzheimer's disease (AD). We profiled acute phase response (APR) proteins (α1-antitrypsin, α1-antichymotrypsin, ceruloplasmin, complement C3, ferritin, α-fibrinogen, β-fibrinogen, γ-fibrinogen, haptoglobin, hemopexin) in CSF of 1291 subjects along the clinical and biomarker spectrum of AD to investigate the association between inflammatory changes, disease outcomes, and demographic variables. Subjects were stratified by Aβ<sub>42</sub>/t-tau as well as the following clinical diagnoses: cognitively normal (CN); subjective cognitive decline (SCD); mild cognitive impairment (MCI); and AD dementia. In separate multiple regressions (adjusting for diagnosis, age, sex, APOE-ε4) of each APR protein and a composite of all APR proteins, CSF Aβ<sub>42</sub>/t-tau status was associated with elevated ferritin, but not any other APR protein in CN and SCD subjects. Rather, the APR was elevated along with symptomatic progression (CN &lt; SCD &lt; MCI &lt; AD), and this was elevation was mediated by CSF p-tau181. APOE ε4 status did not affect levels of any APR proteins in CSF, while these were elevated in males and with increased age. The performance of the APR in predicting clinical diagnosis was influenced by APOE ε4 status, sex, and age. These data provide new insight into inflammatory changes in AD and how this intersects with pathology changes and patient demographics.</p>}},
  author       = {{Ayton, Scott and Janelidze, Shorena and Roberts, Blaine and Palmqvist, Sebastian and Kalinowski, Pawel and Diouf, Ibrahima and Belaidi, Abdel A. and Stomrud, Erik and Bush, Ashley I. and Hansson, Oskar}},
  issn         = {{0301-0082}},
  keywords     = {{acute phase response; Alzheimer's disease; biomarkers; Neuroinflammation}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Progress in Neurobiology}},
  title        = {{Acute phase markers in CSF reveal inflammatory changes in Alzheimer's disease that intersect with pathology, APOE ε4, sex and age}},
  url          = {{http://dx.doi.org/10.1016/j.pneurobio.2020.101904}},
  doi          = {{10.1016/j.pneurobio.2020.101904}},
  volume       = {{198}},
  year         = {{2021}},
}