Aβ accumulation in choroid plexus is associated with mitochondrial-induced apoptosis

One of the possible mechanisms involved in beta-amyloid (A beta)-induced neuronal damage is blood-cerebrospinal fluid barrier dysfunction Recently, we have demonstrated that Alzheimer patients have an elevated expression of A beta in the choroid plexus (CP), where it could impair the physiological functions of CP epithelium We Investigated whether these alterations were mediated by mitochondrial dysfunction. a common early pathomechanism in Alzheimer's disease Our main observations were high A beta levels; increased nitric oxide levels, impairment of the activity and assembly of mitochondrial respiratory chain complexes I and IV, and a significant increase in reactive oxygen species and caspase expression in CP epithelial cells treated with A beta Our results also demonstrate a direct relationship between A beta toxicity, increased expression of matrix metalloprotemase-9. and blood cerebrospinal fluid barrier disruption We propose a sequence of pathological steps that link A beta accumulation in CP epithelium with an enhanced nitric oxide production, mitochondrial dysfunction, and up-regulation of matrix metalloprotemase-9, which ultimately lead to cell death, and probably to CSF barrier dysfunction (C) 2008 Elsevier Inc All rights reserved