Elevated expression of urokinase plasminogen activator in rodent models and patients with cerebral amyloid angiopathy

Vervuurt, M.; Zhu, X.Y.; Schrader, J.; Kort, A.M.; Marques, T.M.; Kersten, I.; ... ; Verbeek, M.M. (2022)

Article / Letter to editor

Aims: The aim of this work is to study the association of urokinase plasminogen activator (uPA) with development and progression of cerebral amyloid angiopathy (CAA). Materials and methods: We studied the expression of uPA mRNA by quantitative polymerase chain reaction (qPCR) and co-localisation of uPA with amyloid-beta (A beta) using immunohistochemistry in the cerebral vasculature of rTg-DI rats compared with wild-type (WT) rats and in a sporadic CAA (sCAA) patient and control subject using immunohistochemistry. Cerebrospinal fluid (CSF) uPA levels were measured in rTg-DI and WT rats and in two separate cohorts of sCAA and Dutch-type hereditary CAA (D-CAA) patients and controls, using enzyme-linked immunosorbent assays (ELISA). Results: The presence of uPA was clearly detected in the cerebral vasculature of rTg-DI rats and an sCAA patient but not in WT rats or a non-CAA human control. uPA expression was highly co-localised with microvascular A beta deposits. In rTg-DI rats, uPA mRNA expression was highly elevated at 3 months of age (coinciding with the emergence of microvascular A beta deposition) and sustained up to 12 months of age (with severe microvascular CAA deposition) compared with WT rats. CSF uPA levels were elevated in rTg-DI rats compared with WT rats (p = 0.03), and in sCAA patients compared with controls (after adjustment for age of subjects, p = 0.05 and p = 0.03). No differences in CSF uPA levels were found between asymptomatic and symptomatic D-CAA patients and their respective controls (after age-adjustment, p = 0.09 and p = 0.44). Increased cerebrovascular expression of uPA in CAA correlates with increased quantities of CSF uPA in rTg-DI rats and human CAA patients, suggesting that uPA could serve as a biomarker for CAA.

• amyloid beta
• biomarker
• cerebral amyloid angiopathy
• cerebrospinal fluid
• urokinase plasminogen activator

• All authors: Vervuurt, M.; Zhu, X.Y.; Schrader, J.; Kort, A.M.; Marques, T.M.; Kersten, I.; Ton, A.M.P. van; Abdo, W.F.; Schreuder, F.H.B.M.; Rasing, I.; Terwindt, G.M.; Wermer, M.J.H.; Greenberg, S.M.; Klijn, C.J.M.; Kuiperij, H.B.; Nostrand, W.E. van; Verbeek, M.M.
• Date: 2022-03-09
• Journal: Neuropathology and Applied Neurobiology
• Volume: 48
• Issue: 5
• DOI: doi:c