CSF biomarkers of neuroinflammation and cerebrovascular dysfunction in early Alzheimer disease
Janelidze, Shorena LU ; Mattsson, Niklas LU
; Stomrud, Erik
LU
; Lindberg, Olof
LU
; Palmqvist, Sebastian
LU
; Zetterberg, Henrik
LU
; Blennow, Kaj
LU
and Hansson, Oskar
LU
(2018)
In Neurology
91(9).
p.867-877
- Abstract
Objective To measure CSF levels of biomarkers reflecting microglia and astrocytes activation, neuroinflammation, and cerebrovascular changes and study their associations with the core biomarkers of Alzheimer disease (AD) pathology (β-amyloid [Aβ] and tau), structural imaging correlates, and clinical disease progression over time. Methods The study included cognitively unimpaired elderly (n = 508), patients with mild cognitive impairment (MCI, n = 256), and patients with AD dementia (n = 57) from the longitudinal Swedish BioFINDER cohort. CSF samples were analyzed for YKL-40, interleukin (IL)-6, IL-7, IL-8, IL-15, IP-10, monocyte chemoattractant protein 1, intercellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1),... (More)
Objective To measure CSF levels of biomarkers reflecting microglia and astrocytes activation, neuroinflammation, and cerebrovascular changes and study their associations with the core biomarkers of Alzheimer disease (AD) pathology (β-amyloid [Aβ] and tau), structural imaging correlates, and clinical disease progression over time. Methods The study included cognitively unimpaired elderly (n = 508), patients with mild cognitive impairment (MCI, n = 256), and patients with AD dementia (n = 57) from the longitudinal Swedish BioFINDER cohort. CSF samples were analyzed for YKL-40, interleukin (IL)-6, IL-7, IL-8, IL-15, IP-10, monocyte chemoattractant protein 1, intercellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1), placental growth factor, and fms-related tyrosine kinase 1 (Flt-1). MRI data were available from 677 study participants. Longitudinal clinical assessments were conducted in control individuals and patients with MCI (mean follow-up 3 years, range 1-6 years). Results CSF levels of YKL-40, ICAM-1, VCAM-1, IL-15, and Flt-1 were increased during the preclinical, prodromal, and dementia stages of AD. High levels of these biomarkers were associated with increased CSF levels of total tau, with the associations, especially for YKL-40, being stronger in Aβ-positive individuals. The results were similar for associations between phosphorylated tau and YKL-40, ICAM-1, and VCAM-1. High levels of the biomarkers were also associated with cortical thinning (primarily in the precuneus and superior parietal regions) and with subsequent cognitive deterioration in patients without dementia as measured with Mini-Mental State Examination (YKL-40) and Clinical Dementia Rating Sum of Boxes (YKL-40, ICAM-1, VCAM-1 and IL-15). Finally, higher levels of CSF YKL-40, ICAM-1, and Flt-1 increased risk of development of AD dementia in patients without dementia. Conclusions Neuroinflammation and cerebrovascular dysfunction are early events occurring already at presymptomatic stages of AD and contribute to disease progression.
(Less)
- author
- Janelidze, Shorena
LU
; Mattsson, Niklas
LU
; Stomrud, Erik
LU
; Lindberg, Olof
LU
; Palmqvist, Sebastian
LU
; Zetterberg, Henrik
LU
; Blennow, Kaj
LU
and Hansson, Oskar
LU
- organization
- publishing date
- 2018-07-27
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Neurology
- volume
- 91
- issue
- 9
- pages
- 867 - 877
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- scopus:85052734659
- pmid:30054439
- ISSN
- 0028-3878
- DOI
- 10.1212/WNL.0000000000006082
- language
- English
- LU publication?
- yes
- id
- 7cb27aa2-2877-4c7e-addd-a0844d2e0df6
- date added to LUP
- 2018-09-26 12:18:53
- date last changed
- 2024-06-10 17:20:06
@article{7cb27aa2-2877-4c7e-addd-a0844d2e0df6,
abstract = {{<p>Objective To measure CSF levels of biomarkers reflecting microglia and astrocytes activation, neuroinflammation, and cerebrovascular changes and study their associations with the core biomarkers of Alzheimer disease (AD) pathology (β-amyloid [Aβ] and tau), structural imaging correlates, and clinical disease progression over time. Methods The study included cognitively unimpaired elderly (n = 508), patients with mild cognitive impairment (MCI, n = 256), and patients with AD dementia (n = 57) from the longitudinal Swedish BioFINDER cohort. CSF samples were analyzed for YKL-40, interleukin (IL)-6, IL-7, IL-8, IL-15, IP-10, monocyte chemoattractant protein 1, intercellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1), placental growth factor, and fms-related tyrosine kinase 1 (Flt-1). MRI data were available from 677 study participants. Longitudinal clinical assessments were conducted in control individuals and patients with MCI (mean follow-up 3 years, range 1-6 years). Results CSF levels of YKL-40, ICAM-1, VCAM-1, IL-15, and Flt-1 were increased during the preclinical, prodromal, and dementia stages of AD. High levels of these biomarkers were associated with increased CSF levels of total tau, with the associations, especially for YKL-40, being stronger in Aβ-positive individuals. The results were similar for associations between phosphorylated tau and YKL-40, ICAM-1, and VCAM-1. High levels of the biomarkers were also associated with cortical thinning (primarily in the precuneus and superior parietal regions) and with subsequent cognitive deterioration in patients without dementia as measured with Mini-Mental State Examination (YKL-40) and Clinical Dementia Rating Sum of Boxes (YKL-40, ICAM-1, VCAM-1 and IL-15). Finally, higher levels of CSF YKL-40, ICAM-1, and Flt-1 increased risk of development of AD dementia in patients without dementia. Conclusions Neuroinflammation and cerebrovascular dysfunction are early events occurring already at presymptomatic stages of AD and contribute to disease progression.</p>}},
author = {{Janelidze, Shorena and Mattsson, Niklas and Stomrud, Erik and Lindberg, Olof and Palmqvist, Sebastian and Zetterberg, Henrik and Blennow, Kaj and Hansson, Oskar}},
issn = {{0028-3878}},
language = {{eng}},
month = {{07}},
number = {{9}},
pages = {{867--877}},
publisher = {{Lippincott Williams & Wilkins}},
series = {{Neurology}},
title = {{CSF biomarkers of neuroinflammation and cerebrovascular dysfunction in early Alzheimer disease}},
url = {{http://dx.doi.org/10.1212/WNL.0000000000006082}},
doi = {{10.1212/WNL.0000000000006082}},
volume = {{91}},
year = {{2018}},
}