Association of plasma placental growth factor with white matter hyperintensities in Alzheimer’s disease

Background The global prevalence of dementia, particularly Alzheimer’s disease (AD), is increasing. With the introduction of anti-β-amyloid (Aβ) antibody drugs, the accurate in vivo diagnosis of AD has become crucial. Autopsy studies have shown that AD often coexists with cerebrovascular injury, which may affect cognitive outcomes and the effectiveness of anti-Aβ drugs. Although white matter hyperintensity (WMH) on magnetic resonance imaging (MRI) is an established marker of cerebrovascular injury, no fluid biomarker has been identified. Objective This study investigated the association between WMH severity and fluid biomarkers, including cerebrospinal fluid (CSF) neurofilament light chain and plasma placental growth factor (PlGF) levels. Methods The study included 242 patients from memory clinics, and 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. Results 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. Conclusions Plasma PlGF is a promising marker of cerebrovascular injury in AD.