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Alzheimer's Imaging Consortium.

Tevy Chan1,2,3, Seyyed Ali Hosseini1,2,3, Arthur C Macedo1,2,3

  • 1Montreal Neurological Institute, Montreal, QC, Canada.

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Summary
This summary is machine-generated.

Impaired cerebrospinal fluid (CSF) clearance of Alzheimer's disease (AD) biomarkers like p-tau181 and neurofilament light chain (NfL) is linked to amyloid pathology. This clearance deficit is independent of blood-brain barrier (BBB) dysfunction.

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Gerontology

Background:

  • The ratio of plasma to cerebrospinal fluid (CSF) biomarkers may indicate peptide clearance from the central nervous system (CNS).
  • The relationship between this clearance and blood-brain barrier (BBB) alterations in Alzheimer's disease (AD) is not well understood.
  • Investigating plasma/CSF biomarker ratios and BBB permeability is crucial for understanding AD pathogenesis.

Purpose of the Study:

  • To examine the ratio between plasma and CSF neurofilament light chain (NfL) and p-tau181 in individuals across the AD spectrum.
  • To determine the relationship between these biomarker ratios and BBB permeability.
  • To explore the role of CSF clearance in AD biomarker accumulation.

Main Methods:

  • Analyzed data from 102 participants in the Translational Biomarkers in Aging and Dementia (TRIAD) cohort.
  • Measured plasma and CSF levels of NfL and p-tau181 using Lumipulse G1200.
  • Calculated the CSF/serum albumin quotient as a marker of BBB integrity and used Spearman's correlation to assess associations with amyloid PET SUVR and albumin quotient.

Main Results:

  • Plasma p-tau181/CSF p-tau181 and plasma NfL/CSF NfL ratios were decreased in amyloid-positive, tau-positive (A+T+) individuals, indicating impaired CSF clearance.
  • Increased amyloid burden correlated with reduced plasma/CSF biomarker ratios.
  • No significant correlation was found between plasma/CSF biomarker ratios and the albumin quotient, suggesting CSF clearance is independent of BBB integrity.

Conclusions:

  • Impaired CSF clearance contributes to the accumulation of AD biomarkers in the CNS.
  • This impaired clearance is not associated with BBB dysfunction.
  • CSF clearance represents a potential therapeutic target for AD, necessitating research into enhancing CNS peptide drainage.