ApoE and clusterin CSF levels influence associations between APOE genotype and changes in CSF tau, but not CSF Aβ42, levels in non-demented elderly

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Abstract

Apolipoprotein E (APOE) ε4 genotype is associated with increased cerebral amyloid beta (Aβ) deposition in nondemented elderly and suggested to influence ApoE as well as ApoJ (clusterin [Clu]) and ApoA1 expression. We aimed to assess whether APOE affects early Alzheimer's disease pathophysiology via these apolipoproteins. Cerebrospinal fluid (CSF) ApoE, Clu, ApoA1, and CSF amyloid beta1-42 (Aβ42) and tau levels were assessed in 403 individuals with subjective cognitive decline and mild cognitive impairment using enzyme-linked immunosorbent assay. Whether CSF apolipoprotein levels mediated APOEε4 allele frequency effects on CSF Aβ42 and tau in nondemented elderly was investigated using mediation analysis, with age- and gender-adjusted linear regression analyses. CSF ApoE mediated 48% of the association between APOEε4 and CSF tau, whereas Clu and ApoA1 did not. In addition, CSF Clu partially mediated the relation between CSF ApoE and tau (12%). CSF apolipoproteins did not mediate the inverse relation between APOEε4 and CSF Aβ42, despite a strong association between the latter 2 biomarkers. In summary, our findings suggest that ApoE and Clu are involved in Aβ-independent pathways as part of the cascade leading to Alzheimer pathology.

Original languageEnglish
Pages (from-to)101-109
Number of pages9
JournalNeurobiology of Aging
Volume79
DOIs
Publication statusPublished - Jul 2019

Cite this

@article{6bb55a7c6af14b39a214cefc60634024,
title = "ApoE and clusterin CSF levels influence associations between APOE genotype and changes in CSF tau, but not CSF Aβ42, levels in non-demented elderly",
abstract = "Apolipoprotein E (APOE) ε4 genotype is associated with increased cerebral amyloid beta (Aβ) deposition in nondemented elderly and suggested to influence ApoE as well as ApoJ (clusterin [Clu]) and ApoA1 expression. We aimed to assess whether APOE affects early Alzheimer's disease pathophysiology via these apolipoproteins. Cerebrospinal fluid (CSF) ApoE, Clu, ApoA1, and CSF amyloid beta1-42 (Aβ42) and tau levels were assessed in 403 individuals with subjective cognitive decline and mild cognitive impairment using enzyme-linked immunosorbent assay. Whether CSF apolipoprotein levels mediated APOEε4 allele frequency effects on CSF Aβ42 and tau in nondemented elderly was investigated using mediation analysis, with age- and gender-adjusted linear regression analyses. CSF ApoE mediated 48{\%} of the association between APOEε4 and CSF tau, whereas Clu and ApoA1 did not. In addition, CSF Clu partially mediated the relation between CSF ApoE and tau (12{\%}). CSF apolipoproteins did not mediate the inverse relation between APOEε4 and CSF Aβ42, despite a strong association between the latter 2 biomarkers. In summary, our findings suggest that ApoE and Clu are involved in Aβ-independent pathways as part of the cascade leading to Alzheimer pathology.",
author = "Slot, {Rosalinde E R} and Kester, {Maartje I} and {Van Harten}, {Argonde C} and Wesley Jongbloed and Bouwman, {Femke H} and Teunissen, {Charlotte E} and Philip Scheltens and {van der Flier}, {Wiesje M} and Robert Veerhuis",
note = "Copyright {\circledC} 2019 Elsevier Inc. All rights reserved.",
year = "2019",
month = "7",
doi = "10.1016/j.neurobiolaging.2019.02.017",
language = "English",
volume = "79",
pages = "101--109",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - ApoE and clusterin CSF levels influence associations between APOE genotype and changes in CSF tau, but not CSF Aβ42, levels in non-demented elderly

AU - Slot, Rosalinde E R

AU - Kester, Maartje I

AU - Van Harten, Argonde C

AU - Jongbloed, Wesley

AU - Bouwman, Femke H

AU - Teunissen, Charlotte E

AU - Scheltens, Philip

AU - van der Flier, Wiesje M

AU - Veerhuis, Robert

N1 - Copyright © 2019 Elsevier Inc. All rights reserved.

PY - 2019/7

Y1 - 2019/7

N2 - Apolipoprotein E (APOE) ε4 genotype is associated with increased cerebral amyloid beta (Aβ) deposition in nondemented elderly and suggested to influence ApoE as well as ApoJ (clusterin [Clu]) and ApoA1 expression. We aimed to assess whether APOE affects early Alzheimer's disease pathophysiology via these apolipoproteins. Cerebrospinal fluid (CSF) ApoE, Clu, ApoA1, and CSF amyloid beta1-42 (Aβ42) and tau levels were assessed in 403 individuals with subjective cognitive decline and mild cognitive impairment using enzyme-linked immunosorbent assay. Whether CSF apolipoprotein levels mediated APOEε4 allele frequency effects on CSF Aβ42 and tau in nondemented elderly was investigated using mediation analysis, with age- and gender-adjusted linear regression analyses. CSF ApoE mediated 48% of the association between APOEε4 and CSF tau, whereas Clu and ApoA1 did not. In addition, CSF Clu partially mediated the relation between CSF ApoE and tau (12%). CSF apolipoproteins did not mediate the inverse relation between APOEε4 and CSF Aβ42, despite a strong association between the latter 2 biomarkers. In summary, our findings suggest that ApoE and Clu are involved in Aβ-independent pathways as part of the cascade leading to Alzheimer pathology.

AB - Apolipoprotein E (APOE) ε4 genotype is associated with increased cerebral amyloid beta (Aβ) deposition in nondemented elderly and suggested to influence ApoE as well as ApoJ (clusterin [Clu]) and ApoA1 expression. We aimed to assess whether APOE affects early Alzheimer's disease pathophysiology via these apolipoproteins. Cerebrospinal fluid (CSF) ApoE, Clu, ApoA1, and CSF amyloid beta1-42 (Aβ42) and tau levels were assessed in 403 individuals with subjective cognitive decline and mild cognitive impairment using enzyme-linked immunosorbent assay. Whether CSF apolipoprotein levels mediated APOEε4 allele frequency effects on CSF Aβ42 and tau in nondemented elderly was investigated using mediation analysis, with age- and gender-adjusted linear regression analyses. CSF ApoE mediated 48% of the association between APOEε4 and CSF tau, whereas Clu and ApoA1 did not. In addition, CSF Clu partially mediated the relation between CSF ApoE and tau (12%). CSF apolipoproteins did not mediate the inverse relation between APOEε4 and CSF Aβ42, despite a strong association between the latter 2 biomarkers. In summary, our findings suggest that ApoE and Clu are involved in Aβ-independent pathways as part of the cascade leading to Alzheimer pathology.

U2 - 10.1016/j.neurobiolaging.2019.02.017

DO - 10.1016/j.neurobiolaging.2019.02.017

M3 - Article

VL - 79

SP - 101

EP - 109

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

ER -