Serum Placental Growth Factor as a Marker of Cerebrovascular Disease Burden in Alzheimer’s Disease

Article type: Research Article

Authors: Wu, Liu-Yun^{a; b} | Chong, Joyce R.^{a; b} | Chong, Jenny P.C.^c | Hilal, Saima^{a; b; d} | Venketasubramanian, Narayanaswamy^e | Tan, Boon Yeow^f | Richards, Arthur Mark^{c; g} | Chen, Christopher P.^{a; b} | Lai, Mitchell K.P.^{a; b; *}

Affiliations: [a] Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore | [b] Memory Aging and Cognition Centre, National University Health System, Singapore | [c] Cardiovascular Research Institute, National University Heart Centre, Singapore | [d] Saw Swee Hock School of Public Health, National University of Singapore, Singapore | [e] Raffles Neuroscience Centre, Raffles Hospital, Singapore | [f] St Luke’s Hospital, Singapore | [g] Department of Medicine, National University Health System, Singapore

Correspondence: [*] Correspondence to: Mitchell K.P. Lai, PhD, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Unit 09-01, 14 Medical Drive, Kent Ridge, S117599, Singapore. E-mail: [email protected].

Abstract: Background:Concomitant cerebrovascular diseases (CeVD) have been identified as an important determinant of Alzheimer’s disease (AD) progression. Development of robust blood-based biomarkers will provide critical tools to evaluate prognosis and potential interventional strategies for AD with CeVD. Objective:This study investigated circulating placental growth factor (PlGF), a potent pro-angiogenic factor related to endothelial dysfunction and vascular inflammation, in an Asian memory clinic cohort of non-demented individuals as well as AD, including its associations with neuroimaging markers of CeVD. Methods:109 patients with AD, 76 cognitively impaired with no dementia (CIND), and 56 non-cognitively impaired (NCI) were included in this cross-sectional study. All subjects underwent 3T brain magnetic resonance imaging to assess white matter hyperintensities (WMH), lacunes, cortical infarcts, and cerebral microbleeds (CMBs). Serum PlGF concentrations were measured by electrochemiluminescence immunoassays. Results:Serum PlGF was elevated in AD, but not CIND, compared to the NCI controls. Adjusted concentrations of PlGF were associated with AD only in the presence of significant CeVD. Elevated PlGF was significantly associated with higher burden of WMH and with CMBs in AD patients. Conclusions:Serum PlGF has potential utility as a biomarker for the presence of CeVD, specifically WMH and CMBs, in AD. Further studies are needed to elucidate the underlying pathophysiological mechanisms linking PlGF to CeVD, as well as to further assess PlGF’s clinical utility.

Keywords: Alzheimer’s disease, blood biomarkers, cerebral microbleeds, cerebrovascular disease, placental growth factor, white matter hyperintensities

DOI: 10.3233/JAD-230811

Journal: Journal of Alzheimer's Disease, vol. 97, no. 3, pp. 1289-1298, 2024