Brain-reactive autoantibodies prevalent in human sera increase intraneuronal amyloid-β(1-42) deposition.

Previous studies have reported immunoglobulin-positive neurons in Alzheimer's disease (AD) brains, an observation indicative of blood-brain barrier (BBB) breakdown. Recently, we demonstrated the nearly ubiquitous presence of brain-reactive autoantibodies in human sera. The significance of these observations to AD pathology is unknown.

Abeta peptides can enter the brain through a defective blood-brain barrier and bind selectively to neurons.

We have investigated the possibility that soluble, blood-borne amyloid beta (Abeta) peptides can cross a defective blood-brain barrier (BBB) and interact with neurons in the brain. Immunohistochemical analyses revealed extravasated plasma components, including Abeta42 in 19 of 21 AD brains, but in only 3 of 13 age-matched control brains, suggesting that a defective BBB is common in AD. To more directly test whether blood-borne Abeta peptides can cross a defective BBB, we tracked the fate of fluorescein isothiocyanate (FITC)-labeled Abeta42 and Abeta40 introduced via tail vein injection into mice with a BBB rendered permeable by treatment with pertussis toxin.