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 language | English |
|---|---|
| Pages (from-to) | 101-109 |
| Number of pages | 9 |
| Journal | Neurobiology of Aging |
| Volume | 79 |
| DOIs | |
| Publication status | Published - Jul 2019 |
Cite this
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ApoE and clusterin CSF levels influence associations between APOE genotype and changes in CSF tau, but not CSF Aβ42, levels in non-demented elderly. / Slot, Rosalinde E R; Kester, Maartje I; Van Harten, Argonde C; Jongbloed, Wesley; Bouwman, Femke H; Teunissen, Charlotte E; Scheltens, Philip; van der Flier, Wiesje M; Veerhuis, Robert.
In: Neurobiology of Aging, Vol. 79, 07.2019, p. 101-109.Research output: Contribution to journal › Article › Academic › peer-review
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 -