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

Camilo Bermudez1, Ekaterina I Hofrenning1, Jeffrey L Gunter2

  • 1Mayo Clinic, Rochester, MN, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
PubMed
Summary
This summary is machine-generated.

Disorders in cerebrospinal fluid (CSF) dynamics, like normal-pressure hydrocephalus (NPH), can affect Alzheimer's disease (AD) blood tests. Abnormal plasma amyloid-beta 42 (Aβ42) levels were linked to enlarged subarachnoid space hydrocephalus (DESH), but p-tau217 remained reliable.

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Area of Science:

  • Neurology
  • Biomarker Discovery
  • Neuroimaging

Background:

  • Coexisting Alzheimer's disease (AD) and cerebrospinal fluid (CSF) dynamic disorders, such as normal-pressure hydrocephalus (NPH), can alter CSF Aβ42 levels, complicating AD biomarker interpretation.
  • The influence of CSF dynamics on plasma-based AD biomarkers remains largely unexplored.
  • This study investigated the association between MRI-detected disproportionately enlarged subarachnoid space hydrocephalus (DESH) and mass spectrometry-based plasma AD biomarkers.

Purpose of the Study:

  • To determine if plasma Alzheimer's disease (AD) biomarkers, measured via mass spectrometry, are associated with disproportionately enlarged subarachnoid space hydrocephalus (DESH) identified on MRI.
  • To assess the impact of CSF dynamics on the reliability of plasma AD biomarkers.

Main Methods:

  • Utilized data from 509 participants in the Mayo Clinic Study of Aging, including MRI, Aβ PET scans, and plasma biomarkers (phosphorylated-tau protein 217, Aβ40, Aβ42).
  • Performed age-adjusted logistic regression to evaluate the association between abnormal plasma biomarker levels (p-Tau 217, %p-tau217, Aβ42, Aβ42/40 ratio) and the presence of DESH.
  • DESH classification was based on a validated automated MRI algorithm.

Main Results:

  • Thirty-two participants were identified as DESH-positive.
  • An abnormal plasma Aβ42 level was significantly associated with DESH (OR, 2.56; p=0.018).
  • No significant association was found between DESH and abnormal plasma p-tau217 or %p-tau217. Subgroup analysis revealed that abnormal Aβ42 combined with positive amyloid PET was associated with DESH.

Conclusions:

  • Plasma Aβ42 levels are influenced by CSF dynamics, specifically DESH, consistent with prior CSF studies.
  • Plasma p-tau217 demonstrates robustness against DESH, suggesting its suitability as a biomarker in individuals with abnormal CSF dynamics.
  • Further validation in populations with more severe CSF dynamic disorders is recommended for p-tau217.