Failure of the choroid plexus in Alzheimer's disease

Alzheimer9s disease is a neurodegenerative disorder characterized clinically by cognitive decline and pathologically by amyloid deposition and neurofibrillary changes. These neuropathological hallmarks are accompanied by reactive events including microglial activation and astrogliosis. The inflammatory response in Alzheimer9s disease brains is distinguished by a pro-inflammatory signature involving amyloid peptides, inflammasome signalling and disrupted blood brain barrier. Inflammatory changes are observed also in the cerebrospinal fluid in Alzheimer9s disease. It remains unknown, however, whether the choroid plexus which produces cerebrospinal fluid and guards the brain from peripheral inflammatory insults, contributes to the inflammation and pathogenesis of Alzheimer9s disease. Here we show that the choroid plexus in Alzheimer9s disease exhibits a pro-inflammaotory signature with aberrant protein accumulation, which contribute to the age-dependent inflammatory changes observed in the cerebrospinal fluid. Magnetic resonance imaging reveals that the choroid plexus in patients with Alzheimer9s disease displays pathological signal and increased volume, which inversely correlates with cognitive decline. Our findings suggest that the choroid plexus, being unable to efficiently resolve inflammatory insults over the lifetime, eventually ignites and drives the aberrant inflammatory response observed in Alzheimer9s disease. These findings advance our understanding of the pathogenesis and open new vistas in the diagnostics and therapeutics of Alzheimer9s disease.