Cerebrovascular accumulation and increased blood-brain barrier permeability to circulating Alzheimer's amyloid beta peptide in aged squirrel monkey with cerebral amyloid angiopathy - PubMed (original) (raw)
Cerebrovascular accumulation and increased blood-brain barrier permeability to circulating Alzheimer's amyloid beta peptide in aged squirrel monkey with cerebral amyloid angiopathy
J B Mackic et al. J Neurochem. 1998 Jan.
Free article
Abstract
Senescent squirrel monkey is a valuable model to study pathogenesis of cerebrovascular amyloid angiopathy (CAA). Cerebrovascular sequestration and blood-brain barrier (BBB) permeability to 121I-amyloid beta(1-40) synthetic peptide (sA beta(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 sA beta(1-40), t(1/2)e, was prolonged by 0.6 h, the systemic clearance, ClSS, 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 sA beta(1-40) was significant, and the BBB permeability was 18.6-fold higher than for inulin. In aged monkey, the sequestration of intact sA beta(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 sA beta(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 sA beta(1-40), and reduced peripheral metabolism, may act in concert with BBB mechanisms, i.e., increased transendothelial transport and microvascular accumulation of blood-borne sA beta(1-40), and reduced brain metabolism to enhance the development of CAA.
Similar articles
- Circulating amyloid-beta peptide crosses the blood-brain barrier in aged monkeys and contributes to Alzheimer's disease lesions.
Mackic JB, Bading J, Ghiso J, Walker L, Wisniewski T, Frangione B, Zlokovic BV. Mackic JB, et al. Vascul Pharmacol. 2002 Jun;38(6):303-13. doi: 10.1016/s1537-1891(02)00198-2. Vascul Pharmacol. 2002. PMID: 12529925 - Isoform-specific effects of apolipoproteins E2, E3, and E4 on cerebral capillary sequestration and blood-brain barrier transport of circulating Alzheimer's amyloid beta.
Martel CL, Mackic JB, Matsubara E, Governale S, Miguel C, Miao W, McComb JG, Frangione B, Ghiso J, Zlokovic BV. Martel CL, et al. J Neurochem. 1997 Nov;69(5):1995-2004. doi: 10.1046/j.1471-4159.1997.69051995.x. J Neurochem. 1997. PMID: 9349544 - Brain clearance of Alzheimer's amyloid-beta40 in the squirrel monkey: a SPECT study in a primate model of cerebral amyloid angiopathy.
Bading JR, Yamada S, Mackic JB, Kirkman L, Miller C, Calero M, Ghiso J, Frangione B, Zlokovic BV. Bading JR, et al. J Drug Target. 2002 Jun;10(4):359-68. doi: 10.1080/10611860290031831. J Drug Target. 2002. PMID: 12164385 - Animal models of cerebral beta-amyloid angiopathy.
Walker LC. Walker LC. Brain Res Brain Res Rev. 1997 Sep 30;25(1):70-84. doi: 10.1016/s0165-0173(97)00017-9. Brain Res Brain Res Rev. 1997. PMID: 9370051 Review.
Cited by
- Age-Dependent Changes in the Plasma and Brain Pharmacokinetics of Amyloid-β Peptides and Insulin.
Zhou AL, Sharda N, Sarma VV, Ahlschwede KM, Curran GL, Tang X, Poduslo JF, Kalari KR, Lowe VJ, Kandimalla KK. Zhou AL, et al. J Alzheimers Dis. 2022;85(3):1031-1044. doi: 10.3233/JAD-215128. J Alzheimers Dis. 2022. PMID: 34924382 Free PMC article. - Guidance on the risk assessment of substances present in food intended for infants below 16 weeks of age.
EFSA Scientific Committee; Hardy A, Benford D, Halldorsson T, Jeger MJ, Knutsen HK, More S, Naegeli H, Noteborn H, Ockleford C, Ricci A, Rychen G, Schlatter JR, Silano V, Solecki R, Turck D, Bresson JL, Dusemund B, Gundert-Remy U, Kersting M, Lambré C, Penninks A, Tritscher A, Waalkens-Berendsen I, Woutersen R, Arcella D, Court Marques D, Dorne JL, Kass GE, Mortensen A. EFSA Scientific Committee, et al. EFSA J. 2017 May 31;15(5):e04849. doi: 10.2903/j.efsa.2017.4849. eCollection 2017 May. EFSA J. 2017. PMID: 32625502 Free PMC article. - Single-cell RNA sequencing identifies senescent cerebromicrovascular endothelial cells in the aged mouse brain.
Kiss T, Nyúl-Tóth Á, Balasubramanian P, Tarantini S, Ahire C, DelFavero J, Yabluchanskiy A, Csipo T, Farkas E, Wiley G, Garman L, Csiszar A, Ungvari Z. Kiss T, et al. Geroscience. 2020 Apr;42(2):429-444. doi: 10.1007/s11357-020-00177-1. Epub 2020 Mar 31. Geroscience. 2020. PMID: 32236824 Free PMC article. - Hypertension impairs neurovascular coupling and promotes microvascular injury: role in exacerbation of Alzheimer's disease.
Csiszar A, Tarantini S, Fülöp GA, Kiss T, Valcarcel-Ares MN, Galvan V, Ungvari Z, Yabluchanskiy A. Csiszar A, et al. Geroscience. 2017 Aug;39(4):359-372. doi: 10.1007/s11357-017-9991-9. Epub 2017 Aug 29. Geroscience. 2017. PMID: 28853030 Free PMC article. - Peripheral complement interactions with amyloid β peptide in Alzheimer's disease: 2. Relationship to amyloid β immunotherapy.
Crane A, Brubaker WD, Johansson JU, Trigunaite A, Ceballos J, Bradt B, Glavis-Bloom C, Wallace TL, Tenner AJ, Rogers J. Crane A, et al. Alzheimers Dement. 2018 Feb;14(2):243-252. doi: 10.1016/j.jalz.2017.04.015. Epub 2017 Jul 26. Alzheimers Dement. 2018. PMID: 28755839 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical