Platelet-derived growth factor-BB and white matter hyperintensity burden in carriers.

BACKGROUND

The apolipoprotein-e4 () gene increases risk for developing late-onset Alzheimer's disease (AD) and has been linked to increased microvascular dysfunction, including pericyte degeneration and blood-brain barrier breakdown. Platelet-derived growth factor-BB (PDGF-BB) is a glycoprotein involved in blood-brain barrier and pericyte maintenance. Increased PDGF-BB levels have been reported in white matter in AD brain tissue. However, the association between circulating levels of PDGF-BB and cerebral white matter damage in older adults remains unknown.

METHODS

Participants included community-dwelling older adults (age range 55-90 years, = 73.1 years; SD =7.5; 61.0% male) from the Alzheimer's Disease Neuroimaging Initiative who underwent venipuncture and blood plasma immunoassay for PDGF-BB, brain MRI scanning with T2-FLAIR for volumetric quantification of white matter hyperintensities (WMH) and genotyping ( = 64). Linear regression analyses examined the relationship between plasma PDGF-BB levels and WMH volume, adjusting for age, sex, intracranial volume (ICV) and stratifying by status.

RESULTS

Greater levels of circulating PDGF-BB were related to greater WMH volume, even after accounting for age, sex, ICV and carrier status ( = 0.040). Nineteen (29.2%) were carriers. When stratified by status, the relationship between PDGF-BB and WMH volume was only significant for carriers ( = 0.007), but not non-carriers ( = 0.448), after adjusting for age, sex and ICV.

DISCUSSION

These findings reveal a differential relationship between PDGF-BB and WMH volume for carriers versus non-carriers. The variant leads to accelerated cerebrovascular injury and cognitive decline. Elevated levels of PDGF-BB in carriers may suggest a role for pericytes and blood-brain barrier dysfunction in white matter damage, vascular cognitive impairment and AD. Additional studies will elucidate the role of PDGF ligands and receptors in these conditions.