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Microglial Markers are Elevated in the Prodromal Phase of Alzheimer's Disease and Vascular Dementia

Olsson, Bob; Hertze, Joakim LU ; Lautner, Ronald; Zetterberg, Henrik; Nägga, Katarina LU ; Hoglund, Kina; Basun, Hans; Annas, Peter; Lannfelt, Lars and Andreasen, Niels, et al. (2013) In Journal of Alzheimer's Disease 33(1). p.45-53
Abstract
Microglia manage immunosurveillance and mediate inflammation, both suggested to be important in Alzheimer's disease (AD). The aim of this study was to investigate if microglial markers could differentiate, firstly between AD and controls, and secondly between stable mild cognitive impairment (MCI) and those progressing to AD and vascular dementia (VaD). Furthermore, we investigated if these markers were sufficiently stable to be used in clinical trials. We quantified YKL-40 and sCD14 in cerebrospinal fluid (CSF) from 96 AD patients, 65 healthy controls, and 170 patients with MCI from baseline and over 5.7 years. For the stability analysis, two CSF samples were collected from 52 AD patients with a six-month interval in between. YKL-40, but... (More)
Microglia manage immunosurveillance and mediate inflammation, both suggested to be important in Alzheimer's disease (AD). The aim of this study was to investigate if microglial markers could differentiate, firstly between AD and controls, and secondly between stable mild cognitive impairment (MCI) and those progressing to AD and vascular dementia (VaD). Furthermore, we investigated if these markers were sufficiently stable to be used in clinical trials. We quantified YKL-40 and sCD14 in cerebrospinal fluid (CSF) from 96 AD patients, 65 healthy controls, and 170 patients with MCI from baseline and over 5.7 years. For the stability analysis, two CSF samples were collected from 52 AD patients with a six-month interval in between. YKL-40, but not sCD14, was significantly elevated in AD compared with healthy controls (p=0.003). Furthermore, YKL-40 and sCD14 were increased in MCI patients who converted to VaD (p=0.029 and p=0.008), but not to AD according to NINCDS-ADRDA. However, when stratified according to CSF levels of tau and A beta(42), YKL-40 was elevated in those with an AD-indicative profile compared with stable MCI with a normal profile (p=0.037). In addition, YKL-40 and sCD14 were very stable in AD patients with good correlation between time-points (r=0.94, p=3.4x10(-25); r=0.77, p=2.0x10(-11)) and the cortical damage marker T-tau. Thus, microglial markers are stable and may be used as safety markers for monitoring CNS inflammation and microglia activation in clinical trials. Moreover, YKL-40 differentiates between AD and controls and between stable MCI and those that convert to AD and VaD. (Less)
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Contribution to journal
publication status
published
subject
keywords
Alzheimer's disease, biomarker, cerebrospinal fluid, dementia, microglia, vascular dementia
in
Journal of Alzheimer's Disease
volume
33
issue
1
pages
45 - 53
publisher
IOS Press
external identifiers
  • wos:000312154400007
  • scopus:84872435139
ISSN
1387-2877
DOI
10.3233/JAD-2012-120787
language
English
LU publication?
yes
id
6a2386ad-66a9-454c-b31d-0fe835e0c262 (old id 3400964)
date added to LUP
2013-02-01 07:06:04
date last changed
2019-07-09 01:13:16
@article{6a2386ad-66a9-454c-b31d-0fe835e0c262,
  abstract     = {Microglia manage immunosurveillance and mediate inflammation, both suggested to be important in Alzheimer's disease (AD). The aim of this study was to investigate if microglial markers could differentiate, firstly between AD and controls, and secondly between stable mild cognitive impairment (MCI) and those progressing to AD and vascular dementia (VaD). Furthermore, we investigated if these markers were sufficiently stable to be used in clinical trials. We quantified YKL-40 and sCD14 in cerebrospinal fluid (CSF) from 96 AD patients, 65 healthy controls, and 170 patients with MCI from baseline and over 5.7 years. For the stability analysis, two CSF samples were collected from 52 AD patients with a six-month interval in between. YKL-40, but not sCD14, was significantly elevated in AD compared with healthy controls (p=0.003). Furthermore, YKL-40 and sCD14 were increased in MCI patients who converted to VaD (p=0.029 and p=0.008), but not to AD according to NINCDS-ADRDA. However, when stratified according to CSF levels of tau and A beta(42), YKL-40 was elevated in those with an AD-indicative profile compared with stable MCI with a normal profile (p=0.037). In addition, YKL-40 and sCD14 were very stable in AD patients with good correlation between time-points (r=0.94, p=3.4x10(-25); r=0.77, p=2.0x10(-11)) and the cortical damage marker T-tau. Thus, microglial markers are stable and may be used as safety markers for monitoring CNS inflammation and microglia activation in clinical trials. Moreover, YKL-40 differentiates between AD and controls and between stable MCI and those that convert to AD and VaD.},
  author       = {Olsson, Bob and Hertze, Joakim and Lautner, Ronald and Zetterberg, Henrik and Nägga, Katarina and Hoglund, Kina and Basun, Hans and Annas, Peter and Lannfelt, Lars and Andreasen, Niels and Minthon, Lennart and Blennow, Kaj and Hansson, Oskar},
  issn         = {1387-2877},
  keyword      = {Alzheimer's disease,biomarker,cerebrospinal fluid,dementia,microglia,vascular dementia},
  language     = {eng},
  number       = {1},
  pages        = {45--53},
  publisher    = {IOS Press},
  series       = {Journal of Alzheimer's Disease},
  title        = {Microglial Markers are Elevated in the Prodromal Phase of Alzheimer's Disease and Vascular Dementia},
  url          = {http://dx.doi.org/10.3233/JAD-2012-120787},
  volume       = {33},
  year         = {2013},
}