Associations of plasma clusterin and Alzheimer’s disease-related MRI markers in adults at mid-life

The CARDIA Brain MRI sub-study

Thaddeus Haight, R. Nick Bryan, Osorio Meirelles, Russell Tracy, Myriam Fornage, Melissa Richard, Ilya Nasrallah, Kristine Yaffe, David R. Jacobs, Cora Lewis, Pamela Schreiner, Stephen Sidney, Christos Davatzikos, Lenore J. Launer

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background Clinical and epidemiological studies of older persons have implicated clusterin in Alzheimer’s disease (AD) pathogenesis. In the context of identifying early biomarkers of risk, we examined associations of plasma clusterin and characteristics of AD in middle-aged individuals from the community. Materials and methods Subjects were 639 cognitively normal individuals (mean age 50 ± 3.5) from the Coronary Artery Risk Development in Young Adults (CARDIA) Brain MRI sub-study. Clusterin was quantified using ELISA (mean 255± 31 ng/ml). Associations were assessed between clusterin and volumes of brain regions known to atrophy in early AD, including entorhinal cortex (ECV), hippocampus (HV), and medial temporal lobe (MTLV) volumes (cm3). Total brain volume (TBV) and volumes of structures affected in later AD were examined for comparison. Results In multivariable models, higher clusterin had a negative non-linear association with ECV (combined left and right hemispheres), and this association was influenced by the highest clusterin levels. Compared to mean clusterin, 1 and 2 standard deviation (SD) level increases in clusterin were associated with -2.1% (95% CI: -3.3,-0.9) and -7.3% (95% CI: -11.3,-3.3) lower ECV, respectively. Similar relationships were observed between clusterin and HV, although the relationship was stronger for left-side HV than the right-side. However, the association was not significant after adjusting for covariates. Negative non-linear associations between clusterin and MTLV were strongest for the left side: compared to mean clusterin, 1 and 2 SD level increases in clusterin were associated with -0.9% (95% CI: -1.9, 0.1) and -3.7% (95% CI: -7.1, -0.3) lower MTLV. There were no significant associations between clusterin and brain structures affected in later AD. Conclusions In middle-aged adults unselected for AD, plasma clusterin was associated with lower volume of the entorhinal cortex, an area that atrophies early in AD. Clusterin could be informative as part of a multi-component preclinical marker for AD.

Original languageEnglish (US)
Article numbere0190478
JournalPloS one
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2018

Fingerprint

Clusterin
coronary vessels
Alzheimer disease
young adults
Magnetic resonance imaging
Young Adult
Brain
Coronary Vessels
Alzheimer Disease
brain
Plasmas
middle-aged adults
atrophy
Entorhinal Cortex
cortex
Association reactions
hippocampus
Atrophy
epidemiological studies
clinical trials

PubMed: MeSH publication types

  • Journal Article
  • Research Support, U.S. Gov't, P.H.S.

Cite this

Haight, T., Bryan, R. N., Meirelles, O., Tracy, R., Fornage, M., Richard, M., ... Launer, L. J. (2018). Associations of plasma clusterin and Alzheimer’s disease-related MRI markers in adults at mid-life: The CARDIA Brain MRI sub-study. PloS one, 13(1), [e0190478]. https://doi.org/10.1371/journal.pone.0190478

Associations of plasma clusterin and Alzheimer’s disease-related MRI markers in adults at mid-life : The CARDIA Brain MRI sub-study. / Haight, Thaddeus; Bryan, R. Nick; Meirelles, Osorio; Tracy, Russell; Fornage, Myriam; Richard, Melissa; Nasrallah, Ilya; Yaffe, Kristine; Jacobs, David R.; Lewis, Cora; Schreiner, Pamela; Sidney, Stephen; Davatzikos, Christos; Launer, Lenore J.

In: PloS one, Vol. 13, No. 1, e0190478, 01.01.2018.

Research output: Contribution to journalArticle

Haight, T, Bryan, RN, Meirelles, O, Tracy, R, Fornage, M, Richard, M, Nasrallah, I, Yaffe, K, Jacobs, DR, Lewis, C, Schreiner, P, Sidney, S, Davatzikos, C & Launer, LJ 2018, 'Associations of plasma clusterin and Alzheimer’s disease-related MRI markers in adults at mid-life: The CARDIA Brain MRI sub-study', PloS one, vol. 13, no. 1, e0190478. https://doi.org/10.1371/journal.pone.0190478
Haight, Thaddeus ; Bryan, R. Nick ; Meirelles, Osorio ; Tracy, Russell ; Fornage, Myriam ; Richard, Melissa ; Nasrallah, Ilya ; Yaffe, Kristine ; Jacobs, David R. ; Lewis, Cora ; Schreiner, Pamela ; Sidney, Stephen ; Davatzikos, Christos ; Launer, Lenore J. / Associations of plasma clusterin and Alzheimer’s disease-related MRI markers in adults at mid-life : The CARDIA Brain MRI sub-study. In: PloS one. 2018 ; Vol. 13, No. 1.
@article{0cc9f576512c4a4eb53d079da11d4f2e,
title = "Associations of plasma clusterin and Alzheimer’s disease-related MRI markers in adults at mid-life: The CARDIA Brain MRI sub-study",
abstract = "Background Clinical and epidemiological studies of older persons have implicated clusterin in Alzheimer’s disease (AD) pathogenesis. In the context of identifying early biomarkers of risk, we examined associations of plasma clusterin and characteristics of AD in middle-aged individuals from the community. Materials and methods Subjects were 639 cognitively normal individuals (mean age 50 ± 3.5) from the Coronary Artery Risk Development in Young Adults (CARDIA) Brain MRI sub-study. Clusterin was quantified using ELISA (mean 255± 31 ng/ml). Associations were assessed between clusterin and volumes of brain regions known to atrophy in early AD, including entorhinal cortex (ECV), hippocampus (HV), and medial temporal lobe (MTLV) volumes (cm3). Total brain volume (TBV) and volumes of structures affected in later AD were examined for comparison. Results In multivariable models, higher clusterin had a negative non-linear association with ECV (combined left and right hemispheres), and this association was influenced by the highest clusterin levels. Compared to mean clusterin, 1 and 2 standard deviation (SD) level increases in clusterin were associated with -2.1{\%} (95{\%} CI: -3.3,-0.9) and -7.3{\%} (95{\%} CI: -11.3,-3.3) lower ECV, respectively. Similar relationships were observed between clusterin and HV, although the relationship was stronger for left-side HV than the right-side. However, the association was not significant after adjusting for covariates. Negative non-linear associations between clusterin and MTLV were strongest for the left side: compared to mean clusterin, 1 and 2 SD level increases in clusterin were associated with -0.9{\%} (95{\%} CI: -1.9, 0.1) and -3.7{\%} (95{\%} CI: -7.1, -0.3) lower MTLV. There were no significant associations between clusterin and brain structures affected in later AD. Conclusions In middle-aged adults unselected for AD, plasma clusterin was associated with lower volume of the entorhinal cortex, an area that atrophies early in AD. Clusterin could be informative as part of a multi-component preclinical marker for AD.",
author = "Thaddeus Haight and Bryan, {R. Nick} and Osorio Meirelles and Russell Tracy and Myriam Fornage and Melissa Richard and Ilya Nasrallah and Kristine Yaffe and Jacobs, {David R.} and Cora Lewis and Pamela Schreiner and Stephen Sidney and Christos Davatzikos and Launer, {Lenore J.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1371/journal.pone.0190478",
language = "English (US)",
volume = "13",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "1",

}

TY - JOUR

T1 - Associations of plasma clusterin and Alzheimer’s disease-related MRI markers in adults at mid-life

T2 - The CARDIA Brain MRI sub-study

AU - Haight, Thaddeus

AU - Bryan, R. Nick

AU - Meirelles, Osorio

AU - Tracy, Russell

AU - Fornage, Myriam

AU - Richard, Melissa

AU - Nasrallah, Ilya

AU - Yaffe, Kristine

AU - Jacobs, David R.

AU - Lewis, Cora

AU - Schreiner, Pamela

AU - Sidney, Stephen

AU - Davatzikos, Christos

AU - Launer, Lenore J.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background Clinical and epidemiological studies of older persons have implicated clusterin in Alzheimer’s disease (AD) pathogenesis. In the context of identifying early biomarkers of risk, we examined associations of plasma clusterin and characteristics of AD in middle-aged individuals from the community. Materials and methods Subjects were 639 cognitively normal individuals (mean age 50 ± 3.5) from the Coronary Artery Risk Development in Young Adults (CARDIA) Brain MRI sub-study. Clusterin was quantified using ELISA (mean 255± 31 ng/ml). Associations were assessed between clusterin and volumes of brain regions known to atrophy in early AD, including entorhinal cortex (ECV), hippocampus (HV), and medial temporal lobe (MTLV) volumes (cm3). Total brain volume (TBV) and volumes of structures affected in later AD were examined for comparison. Results In multivariable models, higher clusterin had a negative non-linear association with ECV (combined left and right hemispheres), and this association was influenced by the highest clusterin levels. Compared to mean clusterin, 1 and 2 standard deviation (SD) level increases in clusterin were associated with -2.1% (95% CI: -3.3,-0.9) and -7.3% (95% CI: -11.3,-3.3) lower ECV, respectively. Similar relationships were observed between clusterin and HV, although the relationship was stronger for left-side HV than the right-side. However, the association was not significant after adjusting for covariates. Negative non-linear associations between clusterin and MTLV were strongest for the left side: compared to mean clusterin, 1 and 2 SD level increases in clusterin were associated with -0.9% (95% CI: -1.9, 0.1) and -3.7% (95% CI: -7.1, -0.3) lower MTLV. There were no significant associations between clusterin and brain structures affected in later AD. Conclusions In middle-aged adults unselected for AD, plasma clusterin was associated with lower volume of the entorhinal cortex, an area that atrophies early in AD. Clusterin could be informative as part of a multi-component preclinical marker for AD.

AB - Background Clinical and epidemiological studies of older persons have implicated clusterin in Alzheimer’s disease (AD) pathogenesis. In the context of identifying early biomarkers of risk, we examined associations of plasma clusterin and characteristics of AD in middle-aged individuals from the community. Materials and methods Subjects were 639 cognitively normal individuals (mean age 50 ± 3.5) from the Coronary Artery Risk Development in Young Adults (CARDIA) Brain MRI sub-study. Clusterin was quantified using ELISA (mean 255± 31 ng/ml). Associations were assessed between clusterin and volumes of brain regions known to atrophy in early AD, including entorhinal cortex (ECV), hippocampus (HV), and medial temporal lobe (MTLV) volumes (cm3). Total brain volume (TBV) and volumes of structures affected in later AD were examined for comparison. Results In multivariable models, higher clusterin had a negative non-linear association with ECV (combined left and right hemispheres), and this association was influenced by the highest clusterin levels. Compared to mean clusterin, 1 and 2 standard deviation (SD) level increases in clusterin were associated with -2.1% (95% CI: -3.3,-0.9) and -7.3% (95% CI: -11.3,-3.3) lower ECV, respectively. Similar relationships were observed between clusterin and HV, although the relationship was stronger for left-side HV than the right-side. However, the association was not significant after adjusting for covariates. Negative non-linear associations between clusterin and MTLV were strongest for the left side: compared to mean clusterin, 1 and 2 SD level increases in clusterin were associated with -0.9% (95% CI: -1.9, 0.1) and -3.7% (95% CI: -7.1, -0.3) lower MTLV. There were no significant associations between clusterin and brain structures affected in later AD. Conclusions In middle-aged adults unselected for AD, plasma clusterin was associated with lower volume of the entorhinal cortex, an area that atrophies early in AD. Clusterin could be informative as part of a multi-component preclinical marker for AD.

UR - http://www.scopus.com/inward/record.url?scp=85040320994&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85040320994&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0190478

DO - 10.1371/journal.pone.0190478

M3 - Article

VL - 13

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 1

M1 - e0190478

ER -