AbstractBackgroundPrevious studies have shown that cerebrospinal fluid (CSF) levels of different biomarkers of neuroinflammation and cerebrovascular dysfunction are increased in Alzheimer’s disease (AD), even during its preclinical and prodromal stages. However, little is known about associations between inflammatory markers and signs of cerebrovascular injury such as white matter lesions (WML) detected with magnetic resonance imaging (MRI) so far.Method582 cognitively unimpaired (CU) elderly and 279 patients with mild cognitive impairment (MCI) from the Swedish BioFINDER cohort were included. CSF samples were analyzed for interleukin (IL)–6, IL‐7, IL‐8, IL‐15, IL‐16, interferon‐gamma induced protein‐10 (IP‐10), monocyte chemoattractant protein 1 (MCP1), intercellular adhesion molecule 1(ICAM‐1), vascular adhesion molecule 1 (VCAM‐1), placental growth factor (PIGF), and fms‐related tyrosine kinase 1 (Flt‐1) as well as vascular endothelial growth factor (VEGF). WML volumes were determined from MRI for all subjects.ResultMore WML was associated with higher levels of IL‐6 (β=0.311, p=0.002), higher levels of IL‐8 (β=0.001, p=0.001), higher levels of PIGF (β=0.007, p<0.001), lower levels of sFLT1 (β=‐0.017, p<0.001) and higher levels of VEGF (β=0.092, p<0.001) in all patients. In the CU group more WML was associated with higher levels of PIGF (β=0.007, p<0.001) and lower levels of sFLT1 (β=‐0.018, p<0.001), whereas in MCI more WML volume was associated with higher levels of IL16 (β=0.118, p<0.001), higher levels of PIGF (β=0.007, p<0.001), and higher levels of VEGF (β=0.105, p=0.003). The associations with PIGF were seen independent of beta‐amyloid‐status. However, the other associations were mainly seen in beta‐amyloid‐negative subjects (N=179 CU and N=164 MCI). Associations were still significant after corrections for multiple comparisons. No associations were found between WML volume and IL‐7, IL‐15, IP‐10, MCP1, ICAM‐1, and VCAM‐1.ConclusionNeuroinflammation is associated with cerebrovascular injury in prodromal stages of AD, especially the markers of the VEGF family widely expressed in the vascular system.