EVIDENCE OF BLOOD-BRAIN-BARRIER PERMEABILITY LEAKAGE FOR CIRCULATING HUMAN ALZHEIMERS BETA-AMYLOID-(1-42)-PEPTIDE/

BRAINS from patients with Alzheimer's disease contain amyloid plaques which are composed of beta-amyloid peptide and are considered to play a causal role in the neuropathology of this disease. The origin of bet a-amyloid peptide in brain parenchyma and vessels of Alzheimer's disea se patients is not known. This study examined the permeability of the blood-brain barrier to beta-amyloid peptide in rats subjected to singl e or repeated episodes of global cerebral ischaemia followed by i.v. i njections of human synthetic beta-amyloid-(1-42)-peptide. Rats receivi ng beta-amyloid peptide after ischaemia demonstrated multifocal and wi despread accumulation of beta-amyloid peptide in hippocampus, cerebral cortex and occasionally in white matter. beta-Amyloid peptide penetra tion involved arterioles, veins and venules. Neuronal, glial and peric yte bodies were observed filled with beta-amyloid peptide. Direct evid ence that soluble human beta-amyloid-(1-42)-peptide crosses the blood- brain barrier and enters the brain from the circulation is thus provid ed for the first time.