FATE OF CEREBROSPINAL FLUID-BORNE AMYLOID BETA-PEPTIDE - RAPID CLEARANCE INTO BLOOD AND APPRECIABLE ACCUMULATION BY CEREBRAL-ARTERIES

In Alzheimer's disease, the neuritic or senile amyloid plaques in hipp ocampus and association cortex, the diffuse plaques in brain areas suc h as the cerebellum and sensorimotor cortex, and the amyloid deposits in the walls of pial and parenchymal blood vessels are mainly composed of amyloid beta-peptides. In the present study, either soluble 40-res idue amyloid beta-peptide radiolabeled with I-125 (I-sA beta) or [C-14 ]polyethylene glycol ([C-14]PEG, a reference material) was briefly inf used into one lateral ventricle of normal rats. By 3.5 min, 30% of the I-sA beta was cleared from ventricular CSF into blood; another 30% wa s removed over the next 6.5 min. No [C-14]PEG was lost from the CSF-br ain system during the first 5 min, and only 20% was cleared by 10 min. Much of the I-sA beta that reached the subarachnoid space was retaine d by pial arteries and arterioles. Virtually no I-sA beta was found in brain. The clearance of amyloid beta-peptides from the CSF-brain syst em, reported herein for normal rats, may be reduced in Alzheimer's dis ease, thus contributing to amyloid deposition in cerebral tissue and b lood vessels.