Evidence of blood-brain barrier permeability/leakage for circulating human Alzheimer's 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 beta-amyloid peptide in brain parenchyma and vessels of Alzheimer's disease patients is not known. This study examined the permeability of the blood-brain barrier to beta-amyloid peptide in rats subjected to single or repeated episodes of global cerebral ischaemia followed by i.v. injections of human synthetic beta-amyloid-(1-42)-peptide. Rats receiving beta-amyloid peptide after ischaemia demonstrated multifocal and widespread accumulation of beta-amyloid peptide in hippocampus, cerebral cortex and occasionally in white matter. beta-Amyloid peptide penetration involved arterioles, veins and venules. Neuronal, glial and pericyte bodies were observed filled with beta-amyloid peptide. Direct evidence that soluble human beta-amyloid-(1-42)-peptide crosses the blood-brain barrier and enters the brain from the circulation is thus provided for the first time.
Pluta
R
R
Department of Neuropathology, Polish Academy of Sciences, Warsaw, Poland.
Barcikowska
M
M
Januszewski
S
S
Misicka
A
A
Lipkowski
A W
AW
D016229:Amyloid beta-Peptides / Q000097:blood*; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism; D006801:Humans; D009419:Nerve Tissue Proteins / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D009419:Nerve Tissue Proteins