Associations of CSF PDGFRβ With Aging, Blood-Brain Barrier Damage, Neuroinflammation, and Alzheimer Disease Pathologic Changes.
Level 3 - non-randomized controlled study
Cross-sectional biomarker analysis within a prospective clinical cohort
PubMed 37137722 · doi:10.1212/WNL.0000000000207358
What was done
PDGFRβ, a marker of pericyte injury, was measured in the CSF of 771 participants from the Swedish BioFINDER-2 cohort (408 cognitively unimpaired, 175 mild cognitive impairment, 188 dementia; mean age 67 years, 50.1% male). Researchers tested associations of CSF PDGFRβ with Aβ-PET, tau-PET, APOE ε4 genotype, MRI metrics (cortical thickness, white matter lesions, cerebral blood flow), blood-brain barrier (BBB) integrity via CSF/plasma albumin ratio (QAlb), and CSF neuroinflammatory markers (YKL-40, GFAP). Mediation analysis was conducted to evaluate whether PDGFRβ and neuroinflammation accounted for age-related BBB breakdown.
What was found
Higher CSF PDGFRβ was related to older age (b = 19.1, β = 0.5, 95% CI 16-22.2, p < 0.001), increased CSF YKL-40 (b = 3.4, β = 0.5, 95% CI 2.8-3.9, p < 0.001), increased CSF GFAP (b = 27.4, β = 0.4, 95% CI 20.9-33.9, p < 0.001), and worse BBB integrity by QAlb (b = 37.4, β = 0.2, 95% CI 24.9-49.9, p < 0.001). PDGFRβ and neuroinflammatory markers partially mediated the relationship between age and BBB dysfunction (16%-33% of total effect). PDGFRβ showed no significant association with APOE ε4, PET measures of Aβ or tau, cortical thickness, or white matter lesions (p > 0.05).
Why it matters
This study clarifies that pericyte injury correlates with age-related neurovascular unit and BBB disruption alongside astrocytic neuroinflammation, rather than acting as a primary driver of core Alzheimer disease amyloid and tau pathology.
Limits
The cross-sectional design cannot establish the temporal sequence or causality among pericyte loss, BBB permeability, and neuroinflammation. The sample is drawn from a single regional Swedish cohort, potentially limiting generalizability to more diverse populations.
Cited by
- supports Soluble PDGF receptor beta is shed from pericytes into plasma and CSF and serves as a measurable biomarker of pericyte dysfunction in small vessel disease.
- supports Soluble platelet-derived growth factor receptor-beta biomarker validation is ongoing in US clinical cohorts of hundreds to thousands of participants to confirm its elevation with aging and the APOE4 allele.