Skip to main content

APOE4 Copy Number-Dependent Proteomic Changes in the Cerebrospinal Fluid.

Publication ,  Journal Article
Berger, M; Cooter, M; Roesler, AS; Chung, S; Park, J; Modliszewski, JL; VanDusen, KW; Thompson, JW; Moseley, A; Devinney, MJ; Smani, S; Cai, V ...
Published in: J Alzheimers Dis
2021

BACKGROUND: APOE4 has been hypothesized to increase Alzheimer's disease risk by increasing neuroinflammation, though the specific neuroinflammatory pathways involved are unclear. OBJECTIVE: Characterize cerebrospinal fluid (CSF) proteomic changes related to APOE4 copy number. METHODS: We analyzed targeted proteomic data from ADNI CSF samples using a linear regression model adjusting for age, sex, and APOE4 copy number, and additional linear models also adjusting for AD clinical status or for CSF Aβ, tau, or p-tau levels. False discovery rate was used to correct for multiple comparisons correction. RESULTS: Increasing APOE4 copy number was associated with a significant decrease in a CRP peptide level across all five models (q < 0.05 for each), and with significant increases in ALDOA, CH3L1 (YKL-40), and FABPH peptide levels (q < 0.05 for each) except when controlling for AD clinical status or neurodegeneration biomarkers (i.e., CSF tau or p-tau). In all models except the one controlling for CSF Aβ levels, though not statistically significant, there was a consistent inverse direction of association between APOE4 copy number and the levels of all 24 peptides from all 8 different complement proteins measured. The odds of this happening by chance for 24 unrelated peptides would be less than 1 in 16 million. CONCLUSION: Increasing APOE4 copy number was associated with decreased CSF CRP levels across all models, and increased CSF ALDOA, CH3L1, and FABH levels when controlling for CSF Aβ levels. Increased APOE4 copy number may also be associated with decreased CSF complement pathway protein levels, a hypothesis for investigation in future studies.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Alzheimers Dis

DOI

EISSN

1875-8908

Publication Date

2021

Volume

79

Issue

2

Start / End Page

511 / 530

Location

Netherlands

Related Subject Headings

  • Receptors, Immunologic
  • Proteomics
  • Neurology & Neurosurgery
  • Male
  • Humans
  • Fructose-Bisphosphate Aldolase
  • Female
  • DNA Copy Number Variations
  • Chitinase-3-Like Protein 1
  • Biomarkers
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Berger, M., Cooter, M., Roesler, A. S., Chung, S., Park, J., Modliszewski, J. L., … and Alzheimer’s Disease Neuroimaging Initiative, . (2021). APOE4 Copy Number-Dependent Proteomic Changes in the Cerebrospinal Fluid. J Alzheimers Dis, 79(2), 511–530. https://doi.org/10.3233/JAD-200747
Berger, Miles, Mary Cooter, Alexander S. Roesler, Stacey Chung, John Park, Jennifer L. Modliszewski, Keith W. VanDusen, et al. “APOE4 Copy Number-Dependent Proteomic Changes in the Cerebrospinal Fluid.J Alzheimers Dis 79, no. 2 (2021): 511–30. https://doi.org/10.3233/JAD-200747.
Berger M, Cooter M, Roesler AS, Chung S, Park J, Modliszewski JL, et al. APOE4 Copy Number-Dependent Proteomic Changes in the Cerebrospinal Fluid. J Alzheimers Dis. 2021;79(2):511–30.
Berger, Miles, et al. “APOE4 Copy Number-Dependent Proteomic Changes in the Cerebrospinal Fluid.J Alzheimers Dis, vol. 79, no. 2, 2021, pp. 511–30. Pubmed, doi:10.3233/JAD-200747.
Berger M, Cooter M, Roesler AS, Chung S, Park J, Modliszewski JL, VanDusen KW, Thompson JW, Moseley A, Devinney MJ, Smani S, Hall A, Cai V, Browndyke JN, Lutz MW, Corcoran DL, and Alzheimer’s Disease Neuroimaging Initiative. APOE4 Copy Number-Dependent Proteomic Changes in the Cerebrospinal Fluid. J Alzheimers Dis. 2021;79(2):511–530.

Published In

J Alzheimers Dis

DOI

EISSN

1875-8908

Publication Date

2021

Volume

79

Issue

2

Start / End Page

511 / 530

Location

Netherlands

Related Subject Headings

  • Receptors, Immunologic
  • Proteomics
  • Neurology & Neurosurgery
  • Male
  • Humans
  • Fructose-Bisphosphate Aldolase
  • Female
  • DNA Copy Number Variations
  • Chitinase-3-Like Protein 1
  • Biomarkers