Decreased levels of soluble amyloid [beta]-protein precursor and [beta]-amyloid protein in cerebrospinal fluid of patients with systemic lupus erythematosus

• Published in: Arthritis research & therapy 2004-01, Vol.6 (2)
• Main Authors: Trysberg, Estelle, Höglund, Kina, Svenungsson, Elisabet, Blennow, Kaj, Tarkowski, Andrej
• Format: Article
• Language: English
• Subjects: Amyloid beta-protein; Analysis; Care and treatment; Cyclophosphamide; Diagnosis; Dosage and administration; Systemic lupus erythematosus; Transforming growth factors
• ISSN: 1478-6354
• DOI: 10.1186/ar1040

Symptoms originating from the central nervous system (CNS) frequently occur in patients with systemic lupus erythematosus (SLE). These symptoms are extremely diverse, including a state of dementia. The aim of this study was to examine the cerebrospinal fluid (CSF) content of soluble molecules indicating axonal degeneration and amyloidogenesis. One hundred and fourteen patients with SLE and age-matched controls were evaluated clinically, with magnetic resonance imaging of the brain and CSF analyses. Levels of tau, amyloid precursor protein (APP), [beta]-amyloid protein (A[beta]42), and transforming growth factor beta (TGF-[beta]) were all determined using sandwich ELISAs. APP and A[beta]42 levels were significantly decreased in SLE patients irrespective of their CNS involvement, as compared with healthy controls. Patients with neuropsychiatric SLE who underwent a second lumbar puncture following successful cyclophosphamide treatment showed further decreases of A[beta]42. CSF-tau levels were significantly increased in SLE patients showing magnetic resonance imaging-verified brain pathology as compared with SLE patients without such engagement. Importantly, tau levels displayed significant correlation to A[beta]42 levels in the CSF. Finally, TGF-[beta] levels were significantly increased in patients with neuropsychiatric SLE as compared with those without. Low intrathecal levels of A[beta]42 found in SLE patients seem to be a direct consequence of a diminished production of APP, probably mediated by heavy anti-inflammatory/immuno-suppressive therapy. Furthermore, our findings suggest that CSF tau can be used as a biochemical marker for neuronal degeneration in SLE. Finally, the increased TGF-[beta] levels observed may support a notion of an ongoing anti-inflammatory response counteracting tissue injury caused by CNS lupus. Keywords: amyloid precursor protein, [beta]-amyloid protein, cerebrospinal fluid, neuropsychiatric systemic lupus erythematosus, tau