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Cited by 71Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

CSF Apo-E levels associate with cognitive decline and MRI changes

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For the Alzheimer’s Disease Neuroimaging Initiative, Toledo, Jon B., Da, Xiao, Weiner, Michael W., Wolk, David A., Xie, Sharon X., Arnold, Steven E., Davatzikos, Christos +2 more·2014·Acta Neuropathologica
DOI 10.1007/s00401-013-1236-0PMC PMC3988233
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Abstract

Apolipoprotein E (APOE) ε4 allele is the most important genetic risk factor for Alzheimer's disease (AD) and it is thought to do so by modulating levels of its product, apolipoprotein E (Apo-E), and regulating amyloid-β (Aβ) clearance. However, information on clinical and biomarker correlates of Apo-E proteins is scarce. We examined the relationship of cerebrospinal fluid (CSF) and plasma Apo-E protein levels, and APOE genotype to cognition and AD biomarker changes in 311 AD neuroimaging initiative subjects with CSF Apo-E measurements and 565 subjects with plasma Apo-E measurements. At baseline, higher CSF Apo-E levels were associated with higher total and phosphorylated CSF tau levels. CSF Apo-E levels were associated with longitudinal cognitive decline, MCI conversion to dementia, and gray matter atrophy rate in total tau/Aβ1-42 ratio and APOE genotype-adjusted analyses. In analyses stratified by APOE genotype, our results were only significant in the group without the ε4 allele. Baseline CSF Apo-E levels did not predict longitudinal CSF Aβ or tau changes. Plasma Apo-E levels show a mild correlation with CSF Apo-E levels, but were not associated with longitudinal cognitive and MRI changes. Based on our analyses, we speculate that increased CSF Apo-E2 or -E3 levels might represent a protective response to injury in AD and may have neuroprotective effects by decreasing neuronal damage independent of tau and amyloid deposition in addition to its effects on amyloid clearance.

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  • Higher CSF ApoE levels were associated with higher CSF tau levels and cognitive decline in human.

    “higher CSF ApoE levels were associated with higher CSF tau levels and cognitive decline in human [12].”

    From Apolipoprotein E metabolism and functions in brain and its role in Alzheimer's disease (2017) · cites this paper as [12]

    The Abstract reports that higher CSF Apo-E levels were associated with higher total and phosphorylated CSF tau levels. But the Results section on cognitive decline reports that *low*, not high, CSF Apo-E levels were associated with greater longitudinal cognitive decline. The claim is therefore supported for tau but misleading about the direction of the cognitive association. (LLM, conf=0.88)

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References 68 · Cited by 71

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Authors
Initiative, F. T. A. D. N., Toledo, J. B., Da, X., Weiner, M. W., Wolk, D. A., Xie, S. X., Arnold, S. E., Davatzikos, C., Shaw, L. M., & Trojanowski, J. Q.
Affiliations
  • Hospital of the University of Pennsylvania (US)
  • San Francisco VA Medical Center (US)
  • University of Pennsylvania (US)
Corresponding author
Trojanowski, John Q.
ORCID
Venue
Acta Neuropathologica
Publisher
Springer Science and Business Media LLC
Published
2014-01-03
Volume
127
Issue
5
Pages
621-632
ISSN
  • 0001-6322 (ISSN-L)
  • 1432-0533
DOI
10.1007/s00401-013-1236-0
PMC
PMC3988233
OpenAlex
W2024269867
Cited by
71
References
68
Citations by year
2026: 1 · 2025: 4 · 2024: 5 · 2023: 5 · 2022: 7 · 2021: 2 · 2020: 7 · 2019: 9 · 2018: 1 · 2017: 9 · 2016: 7 · 2015: 11 · 2014: 3
FWCI
6.67
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Acta Neuropathologica (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institutes of Health (5u01ag024904-10)
  • Canadian Institutes of Health Research
  • National Institute on Aging (U01-AG-024904, P30AG010129, K01AG030514, P30AG010124, R01AG014971)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
apolipoprotein E, APOE ε4, cerebrospinal fluid biomarkers, Alzheimer's disease, cognitive decline, mild cognitive impairment, conversion to dementia, tau phosphorylation, amyloid-beta, gray matter atrophy, neuroprotection, amyloid clearance
MeSH terms
Aged, Alzheimer Disease, Apolipoproteins E, Atrophy, Brain, Cognition, Female, Follow-Up Studies, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Peptide Fragments, Phosphorylation, Severity of Illness Index, Biomarkers, Survival Analysis, Amyloid beta-Peptides, tau Proteins, Disease Progression, Cognitive Dysfunction, Gray Matter

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