Association of Plasma Placental Growth Factor with White Matter Hyperintensities in Alzheimer’s Disease

Autopsy studies have shown that Alzheimer's disease (AD) often coexists with cerebrovascular injury, affecting cognitive outcomes and the effectiveness of anti-amyloid-beta (Aβ) drugs. No fluid biomarkers of cerebrovascular injury have been identified yet. We investigated the association between white matter hyperintensities (WMH) severity and fluid biomarkers, including cerebrospinal fluid (CSF) neurofilament light chain and plasma placental growth factor (PlGF) levels. This study included 242 patients from memory clinics. Magnetic resonance imaging (MRI), CSF, and plasma samples were collected. Patients were classified as AD+ or non-AD based on the CSF Aβ42/Aβ40 ratio. In the discovery cohort (79 AD+ and 20 non-AD patients with 3D-T1 images), we analyzed the association between WMH volume and plasma PlGF. In the validation cohort (54 AD+ patients without 3D-T1 images), we analyzed the association between WMH grading and plasma PlGF. Among AD+ patients in the discovery cohort, plasma PlGF levels remained significantly associated with WMH volume and grading after adjusting for age, sex, and global cognition. Among the AD+ patients in the validation cohort, the high-PlGF (above median) group had significantly greater WMH volumes and a higher number of patients with a high WMH grading than the low-PlGF (below median) group. Plasma PlGF is a promising marker of cerebrovascular injury in AD.