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Cerebrovascular Accumulation and Increased Blood‐Brain Barrier Permeability to Circulating Alzheimer's Amyloid β Peptide in Aged Squirrel Monkey with Cerebral Amyloid Angiopathy
Author(s) -
Mackic Jasmina B.,
Weiss Martin H.,
Miao Wesley,
Kirkman Erlinda,
Ghiso Jorge,
Calero Miguel,
Bading James,
Frangione Blas,
Zlokovic Berislav V.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.70010210.x
Subject(s) - cerebral amyloid angiopathy , blood–brain barrier , amyloid (mycology) , pathology , medicine , squirrel monkey , amyloid β , neuroscience , biology , disease , anatomy , dementia , central nervous system
Senescent squirrel monkey is a valuable model to study pathogenesis of cerebrovascular amyloid angiopathy (CAA). Cerebrovascular sequestration and blood‐brain barrier (BBB) permeability to 125 I‐amyloid β(1‐40) synthetic peptide (sAβ 1‐40 ) were studied in adult versus aged squirrel monkey 1 h after a single intravenous injection. In aged monkey, the half‐time of elimination of sAβ 1‐40 , t e 1/2 , was prolonged by 0.6 h, the systemic clearance, Cl SS , was reduced from 1.8 to 1.1 ml/min/kg, and the mean residence time of intact peptide in the circulation was increased by 1 h (45%). In adult monkey, cerebrovascular sequestration of intact sAβ 1‐40 was significant, and the BBB permeability was 18.6‐fold higher than for inulin. In aged monkey, the sequestration of intact sAβ 1‐40 by cortical and leptomeningeal microvessels and the BBB permeability were increased by 5.9, 1.8‐, and 2.1‐fold, respectively, in the presence of an unchanged barrier to inulin. In brain parenchyma of aged animals, 76.1% of circulating sAβ 1‐40 remained intact versus 45.7% in adult. We conclude that multiple age‐related systemic effects, i.e., reduced body elimination and systemic clearance of sAβ 1‐40 , and reduced peripheral metabolism, may act in concert with BBB mechanisms, i.e., increased transendothelial transport and microvascular accumulation of blood‐borne sAβ 1‐40 , and reduced brain metabolism to enhance the development of CAA.