Is a breakdown of the blood-brain barrier cause or effect?

Several alternative explanations for the pathogenesis of Alzheimer's disease proposed by Hardy et al. are presented. From our vantage point, the amyloid deposition and alterations in the blood-brain barrier in Alzheimer's disease are less likely related to impaired projections of locus ceruleus, nucleus basalis, and raphé nucleus than to a primary insult to the blood vessels produced by a humoral or cell-mediated immune attack. Such an attack would then be associated with the formation of neuritic plaques which increasingly engulf pre-synaptic and post-synaptic neuronal constituents as well as surrounding glia. Such a process could then interrupt the retrograde trophic effects of post-synaptic cortical cells upon projecting subcortical cells, resulting in degeneration of the projecting cells and impairment of cognitive function characteristic of Alzheimer's disease.