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Cited by 218Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration Mechanisms

Plasma Biomarkers Associated With the Apolipoprotein E Genotype and Alzheimer Disease

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Soares, Holly D.·2012·Archives of Neurology
DOI 10.1001/archneurol.2012.1070PMC PMC3683865
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Abstract

BACKGROUND: A blood-based test that could be used as a screen for Alzheimer disease (AD) may enable early intervention and better access to treatment. OBJECTIVE: To apply a multiplex immunoassay panel to identify plasma biomarkers of AD using plasma samples from the Alzheimer's Disease Neuroimaging Initiative cohort. DESIGN: Cohort study. SETTING: The Biomarkers Consortium Alzheimer's Disease Plasma Proteomics Project. PARTICIPANTS: Plasma samples at baseline and at 1 year were analyzed from 396 (345 at 1 year) patients with mild cognitive impairment, 112 (97 at 1 year) patients with AD, and 58 (54 at 1 year) healthy control subjects. MAIN OUTCOME MEASURES: Multivariate and univariate statistical analyses were used to examine differences across diagnostic groups and relative to the apolipoprotein E (ApoE) genotype. RESULTS: Increased levels of eotaxin 3, pancreatic polypeptide, and N-terminal protein B-type brain natriuretic peptide were observed in patients, confirming similar changes reported in cerebrospinal fluid samples of patients with AD and MCI. Increases in tenascin C levels and decreases in IgM and ApoE levels were also observed. All participants with Apo ε3/ε4 or ε4/ε4 alleles showed a distinct biochemical profile characterized by low C-reactive protein and ApoE levels and by high cortisol, interleukin 13, apolipoprotein B, and gamma interferon levels. The use of plasma biomarkers improved specificity in differentiating patients with AD from controls, and ApoE plasma levels were lowest in patients whose mild cognitive impairment had progressed to dementia. CONCLUSIONS: Plasma biomarker results confirm cerebrospinal fluid studies reporting increased levels of pancreatic polypeptide and N-terminal protein B-type brain natriuretic peptide in patients with AD and mild cognitive impairment. Incorporation of plasma biomarkers yielded high sensitivity with improved specificity, supporting their usefulness as a screening tool. The ApoE genotype was associated with a unique biochemical profile irrespective of diagnosis, highlighting the importance of genotype on blood protein profiles.

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  • Earlier association studies of plasma ApoE level with Alzheimer's disease have reported inconsistent findings.

    “Earlier association studies of plasma ApoE level with AD have reported inconsistent findings [26–31]”

    From Genome-wide analysis identifies novel loci influencing plasma apolipoprotein E concentration and Alzheimer’s disease risk (2023) · cites this paper as [29]

    The Comment section says earlier studies of blood-based biomarkers in AD showed “little consistency across studies” and discusses variability in the literature. It does not specifically say that earlier studies of plasma ApoE levels reported inconsistent findings; its own Results report decreased ApoE levels in AD and MCI comparisons. (LLM, conf=0.82)

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Authors
Soares, H. D.
Affiliations
Bristol-Myers Squibb (United States) (US)
Corresponding author
Soares, Holly D.
ORCID
Soares, Holly D.
Venue
Archives of Neurology
Publisher
American Medical Association (AMA)
Published
2012-10-01
Volume
69
Issue
10
Pages
1310
ISSN
0003-9942 (ISSN-L)
DOI
10.1001/archneurol.2012.1070
PMC
PMC3683865
OpenAlex
W2130006532
Cited by
218
References
5
Citations by year
2026: 5 · 2025: 8 · 2024: 15 · 2023: 13 · 2022: 23 · 2021: 17 · 2020: 13 · 2019: 7 · 2018: 5 · 2017: 11 · 2016: 24 · 2015: 27 · 2014: 23 · 2013: 23 · 2012: 4
FWCI
17.59
Type
journal article
Language
en
Open access
Locations
  • Archives of Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Bristol-Myers Squibb
  • Eli Lilly and Company
  • Pfizer
  • AstraZeneca
  • University of Pennsylvania
  • Eisai
  • National Institutes of Health (5u01ag024904-10)
  • Perelman School of Medicine, University of Pennsylvania
  • Canadian Institutes of Health Research
  • National Institute on Aging (U01-AG-024904, P30AG010129, K01AG030514, P30AG010124, P30AG019610, P30AG013846)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, plasma biomarkers, APOE genotype, mild cognitive impairment, eotaxin-3, pancreatic polypeptide, N-terminal brain natriuretic peptide, tenascin-C, C-reactive protein, cortisol, IL-13, apolipoprotein B, interferon-gamma, blood-based screening, multiplex immunoassay, biomarker profiles
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Analysis of Variance, Apolipoproteins B, Apolipoproteins E, C-Reactive Protein, Female, Genotype, Humans, Immunoassay, Interleukin-3, Male, ROC Curve, Cohort Studies, Biomarkers, Case-Control Studies, Chemokine CXCL9, Cognitive Dysfunction

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