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Related Experiment Video

Updated: Jan 7, 2026

Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies
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Biomarkers.

Lina Lu1, Alexa Pichet Binette1, Shorena Janelidze1

  • 1Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 26, 2025
PubMed
Summary
This summary is machine-generated.

The APOE ε4 allele (APOE4) influences Alzheimer's disease (AD) risk through distinct protein pathways in cerebrospinal fluid and plasma. These findings highlight potential biomarkers for early AD detection and therapeutic targets.

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Area of Science:

  • Neuroscience
  • Genetics
  • Biochemistry

Background:

  • The apolipoprotein E ε4 allele (APOE4) is a significant genetic risk factor for Alzheimer's disease (AD).
  • APOE4 is strongly associated with amyloid-beta (Aβ) pathology, but the underlying mechanisms remain unclear.
  • Proteomics approaches are utilized to identify proteins interacting with APOE4 through Aβ-dependent and independent pathways.

Purpose of the Study:

  • To identify proteins associated with APOE4 in plasma and cerebrospinal fluid (CSF).
  • To investigate the interplay between APOE4, Aβ pathology, and protein expression.
  • To explore potential Aβ-independent and Aβ-dependent mechanisms linking APOE4 to AD.

Main Methods:

  • Proteomic analysis of plasma (SomaLogic 7K) and CSF (Olink Explore3072) from 1,773 and 2,369 participants, respectively.
  • Linear models were used to examine protein associations with APOE4 and Aβ status, adjusting for each other, age, and sex.
  • Mediation analysis identified proteins mediating the effects of APOE4 on Aβ and vice versa.

Main Results:

  • In CSF, 98 proteins associated with APOE4 were identified, with 9 independent of Aβ. Aβ mediated APOE4 effects on 76 proteins.
  • In plasma, 254 proteins associated with APOE4 were identified, with 172 independent of Aβ. Aβ mediated APOE4 effects on 29 proteins.
  • APOE4-protein associations were largely attenuated by Aβ in CSF, but remained significant in plasma, indicating distinct mechanisms.

Conclusions:

  • Distinct proteomic profiles are associated with APOE4 in plasma versus CSF.
  • Complex molecular pathways, both Aβ-dependent and independent, are linked to APOE4.
  • Proteins identified may serve as potential biomarkers for early AD detection and therapeutic targets.