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Comparative Study
. 2003;121(2):487-92.
doi: 10.1016/s0306-4522(03)00474-3.

Efflux of human and mouse amyloid beta proteins 1-40 and 1-42 from brain: impairment in a mouse model of Alzheimer's disease

W A Banks  1 , S M Robinson, S Verma, J E Morley
Affiliations
Comparative Study

Efflux of human and mouse amyloid beta proteins 1-40 and 1-42 from brain: impairment in a mouse model of Alzheimer's disease

W A Banks et al. Neuroscience. 2003.

Abstract

Brain to blood transport is believed to be a major determinant of the amount of amyloid beta protein (AbetaP) found in brain. Impaired efflux has been suggested as a mechanism by which AbetaP can accumulate in the CNS and so lead to Alzheimer's disease (AD). To date, however, no study of the efflux of the form of AbetaP most relevant to AD, AbetaP1-42, has been conducted, even though a single amino acid substitution in AbetaP can greatly alter efflux. Here, we examined the efflux of AbetaP mouse1-42, mouse1-40, human1-42, and human1-40 in young CD-1, young senesence accelerated mouse (SAM) P8, and aged SAMP8 mice. The SAMP8 mouse with aging spontaneously overproduces AbetaP and develops cognitive impairments reversed by AbetaP-directed antibody or phosphorothioate antisense oligonucleotide. CD-1 mice transported all forms of AbetaP, although mouse1-42 and human1-40 were transported faster than the other forms. There was a decrease in the saturable transport of mouse1-42 in SAMP8 mice regardless of age. Efflux of mouse1-40 and human1-42 was only by a non-saturable mechanism in young SAMP8 mice and their efflux was totally absent in aged SAMP8 mice. These differences in the efflux of the various forms of AbetaP among the three groups of mice supports the hypothesis that impaired efflux is an important factor in the accumulation of AbetaP in the CNS.

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Figures

Figure 1
Figure 1
SDS gel of mouse AßP1-42 radioactively labeled with NaI by the chloramine-T method and purified on a column of sephadex G-10.
Figure 2
Figure 2
Efflux of AßPmouse1-42 from the CNS to Blood in CD-1, Young SAMP8, and Aged SAMP8 mice. Upper Panel: The relation between log(%Inj/brain) and time was statistically significant for each group of mice, demonstrating that AßP was cleared from the CNS. Lower Panel: the CD-1 mice cleared mouse1-42 more quickly than the SAMP8 mice.
Figure 3
Figure 3
Saturable Component to the Efflux of AßP mouse1-42 in CD-1, Young SAMP8, and Aged SAMP8 mice. All three groups of mice had a saturable component to efflux.
Figure 4
Figure 4
Slopes of All AßP peptides in Each Group of Mice. A 2-way ANOVA showed statistical significance among the slopes for interaction (p<0.001), a trend for peptide, and no effect for mouse group. Newman-Keuls range test found the statistical differences shown: *p<0.05; **p<0.01.
Figure 5
Figure 5
Effects of Various AßP's on the Efflux of radioactive Mouse1-42. Each of the peptides produced a statistically significant inhibition in the efflux of mouse1-42.
See this image and copyright information in PMC

References

    1. Bacskai BJ, Kajdasz ST, Christie RH, Carter C, Games D, Seubert P, Schenk D, Hyman BT. Imaging of amyloid-β deposits in brains of living mice permits direct observation of clearance of plaques with immunotherapy. Nature Medicine. 2001;7:369–372. - PubMed
    1. Bading JR, Yamada S, Mackic JB, Kirkman L, Miller C, Calero M, Ghiso J, Frangione B, Zlokovic BV. Brain clearance of Alzheimer's amyloid-ß040 in the squirrel monkey: A SPECT study in a primate model of cerebral amyloid angiopathy. J Drug Targeting. 2002;10:359–368. - PubMed
    1. Banks WA, Broadwell RD. Blood to brain and brain to blood passage of native horseradish peroxidase, wheat germ agglutinin and albumin: pharmacokinetic and morphological assessments. J Neurochem. 1994;62:2404–2419. - PubMed
    1. Banks WA, DiPalma CR, Farrell CL. Impaired transport of leptin across the blood-brain barrier in obesity. Peptides. 1999;20:1341–1345. - PubMed
    1. Banks WA, Farr SA, Butt W, Kumar VB, Franko MW, Morley JE. Delivery across the blood-brain barrier of antisense directed againt amyloid β: reversal of learning and memory deficits in mice overexpressing amyloid precursor protein. J Pharmacol Exp Ther. 2001;297:1113–1121. - PubMed

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