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Higher cerebrospinal fluid (CSF) Aβ38 levels correlate with reduced ventricular enlargement in Alzheimer's disease (AD). This suggests Aβ38 may serve as a biomarker for AD progression and CSF clearance.

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Medical Imaging

Background:

  • Alzheimer's disease (AD) pathology involves amyloid-beta (Aβ) peptides, with Aβ42 and its shorter isoform Aβ38 being key.
  • Elevated cerebrospinal fluid (CSF) Aβ38 levels are associated with slower cognitive decline in AD.
  • Ventricular enlargement, indicated by increased lateral ventricle volume (LVV) and choroid plexus volume (CPV), is a hallmark of AD progression.

Purpose of the Study:

  • To investigate the relationship between CSF Aβ38 levels and ventricular volumes (LVV and CPV) in individuals with varying cognitive status.
  • To explore the association of CSF Aβ38 with CSF Aβ42 levels and Aβ-positivity in Alzheimer's disease.

Main Methods:

  • Analysis of 204 individuals from the TRIAD cohort, including cognitively unimpaired (CU), mild cognitive impairment (MCI) due to AD, and AD dementia.
  • Quantification of CSF Aβ38 and Aβ42 using a novel nucleic acid linked immuno-sandwich assay (NULISA).
  • Assessment of Aβ-positivity via Aβ-PET SUVR and measurement of LVV and CPV using FreeSurfer.

Main Results:

  • CSF Aβ38 levels were significantly lower in Aβ-positive individuals compared to Aβ-negative individuals.
  • Increased LVV and CPV were observed in Aβ-positive individuals.
  • CSF Aβ38 levels showed a positive correlation with CSF Aβ42 and a negative correlation with LVV and CPV.

Conclusions:

  • The findings suggest a metabolic link between CSF Aβ38 and Aβ42, potentially involving γ-secretase or BACE1 activity.
  • CSF Aβ38, LVV, and CPV patterns are distinct in Aβ-positive and Aβ-negative individuals, indicating their relevance as AD biomarkers.
  • The inverse correlation between CSF Aβ38 and ventricular volumes suggests a link between macro-CSF production and micro-level Aβ clearance.