BACKGROUND AND OBJECTIVES: Injured pericytes in the neurovascular unit release platelet-derived growth factor β (PDGFRβ) into the cerebrospinal fluid (CSF). However, it is not clear how pericyte injury contributes to Alzheimer's disease (AD)-related changes and blood brain barrier (BBB) damage. We aimed to test if CSF PDGFRβ was associated with different AD- and age-associated pathological changes leading to dementia.

METHODS: PDGFRβ was measured in the CSF of 771 cognitively unimpaired (CU, n=408), mild cognitive impairment (MCI, n=175) and dementia subjects (n=188) from the Swedish BioFINDER-2 cohort. We then checked association Aβ-PET and tau-PET SUVR, APOE ε4 genotype and MRI measurements of cortical thickness, white matter lesions (WML) and cerebral blood flow (CBF). We also analysed the role of CSF PDGFRβ in the relationship between aging, BBB dysfunction (measured by CSF/plasma albumin ratio, QAlb) and neuroinflammation (i.e., CSF levels of YKL-40 and glial fibrillary acidic protein [GFAP], preferentially expressed in reactive astrocytes).

RESULTS: The cohort had a mean age of 67 years (CU=62.8, MCI=69.9, dementia=70.4) and 50.1% were male (CU=46.6%, MCI=53.7%, dementia=54.3%). Higher CSF PDGFRβ concentrations were related to higher age (b=19.1, β=0.5, 95% CI=16-22.2, p<0.001), increased CSF neuroinflammatory markers of glial activation YKL-40 (b=3.4, β=0.5, 95% CI=2.8-3.9, p<0.001) and GFAP (b=27.4, β=0.4, 95% CI=20.9-33.9, p<0.001), and worse BBB integrity measured by QAlb (b=37.4, β=0.2, 95% CI=24.9-49.9, p<0.001). Age was also associated with worse BBB integrity, and this was partly mediated by PDGFRβ and neuroinflammatory markers (16-33% of total effect). However, PDGFRβ showed no associations with APOE ε4 genotype, PET imaging of Aβ and tau pathology or MRI measures of brain atrophy and white matter lesions (p>0.05).

DISCUSSION: In summary, pericyte damage, reflected by CSF PDGFRβ, may be involved in age-related BBB disruption together with neuroinflammation, but is not related to Alzheimer-related pathological changes.

Original languageEnglish
Pages (from-to)E30-E39
Issue number1
Publication statusPublished - 2023 May 3

Bibliographical note


Subject classification (UKÄ)

  • Neurology


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