Amyloid-beta Induces Chemokine Secretion and Monocyte Migration Across a Human Blood--brain Barrier Model

Overview

Journal Mol Med

Publisher Biomed Central

Specialties General Medicine
Molecular Biology

Date 1998 Aug 26

PMID 9713826

Citations 84

Authors

M Fiala

L Zhang

X Gan

B Sherry

D Taub

M C Graves

S Hama

D Way

M Weinand

M Witte

D Lorton

Y M Kuo

A E Roher

Affiliations

Soon will be listed here.

Abstract

Background: Aside from numerous parenchymal and vascular deposits of amyloid beta (A beta) peptide, neurofibrillary tangles, and neuronal and synaptic loss, the neuropathology of Alzheimer's disease is accompanied by a subtle and chronic inflammatory reaction that manifests itself as microglial activation. However, in Alzheimer's disease, alterations in the permeability of the blood-brain barrier and chemotaxis, in part mediated by chemokines and cytokines, may permit the recruitment and transendothelial passage of peripheral cells into the brain parenchyma.

Materials And Methods: Human monocytes from different donors were tested for their capacity to differentiate into macrophages and their ability to secrete cytokines and chemokines in the presence of A beta 1-42. A paradigm of the blood-brain barrier was constructed utilizing human brain endothelial and astroglial cells with the anatomical and physiological characteristics observed in vivo. This model was used to test the ability of monocytes/macrophages to transmigrate when challenged by A beta 1-42 on the brain side of the blood-brain barrier model.

Results: In cultures of peripheral monocytes, A beta 1-42 induced the secretion of proinflammatory cytokines TNF-alpha, IL-6, IL-1 beta, and IL-12, as well as CC chemokines MCP-1, MIP-1 alpha, and MIP-1 beta, and CXC chemokine IL-8 in a dose-related fashion. In the blood-brain barrier model, A beta 1-42 and monocytes on the brain side potentiated monocyte transmigration from the blood side to the brain side. A beta 1-42 stimulated differentiation of monocytes into adherent macrophages in a dose-related fashion. The magnitude of these proinflammatory effects of A beta 1-42 varied dramatically with monocytes from different donors.

Conclusion: In some individuals, circulating monocytes/macrophages, when recruited by chemokines produced by activated microglia and macrophages, could add to the inflammatory destruction of the brain in Alzheimer's disease.

Citing Articles

Brain interleukins and Alzheimer's disease.

Abdelhamed H, Hassan A, Sakraan A, Al-Deeb R, Mousa D, Aboul Ezz H Metab Brain Dis. 2025; 40(2):116.

PMID: 39891777 PMC: 11787210. DOI: 10.1007/s11011-025-01538-5.

Olfactory dysfunction as potential biomarker in neurodegenerative diseases: a narrative review.

De Cleene N, Schwarzova K, Labrecque S, Cerejo C, Djamshidian A, Seppi K Front Neurosci. 2025; 18():1505029.

PMID: 39840019 PMC: 11747286. DOI: 10.3389/fnins.2024.1505029.

The Interplay Between Accumulation of Amyloid-Beta and Tau Proteins, PANoptosis, and Inflammation in Alzheimer's Disease.

Zhuang X, Lin J, Song Y, Ban R, Zhao X, Xia Z Neuromolecular Med. 2025; 27(1):2.

PMID: 39751702 DOI: 10.1007/s12017-024-08815-z.

Endothelial Dysfunctions in Blood-Brain Barrier Breakdown in Alzheimer's Disease: From Mechanisms to Potential Therapies.

Yue Q, Leng X, Xie N, Zhang Z, Yang D, Man Hoi M CNS Neurosci Ther. 2024; 30(11):e70079.

PMID: 39548663 PMC: 11567945. DOI: 10.1111/cns.70079.

Neuroinflammation in Alzheimer's disease: insights from peripheral immune cells.

Zhang Q, Yang G, Luo Y, Jiang L, Chi H, Tian G Immun Ageing. 2024; 21(1):38.

PMID: 38877498 PMC: 11177389. DOI: 10.1186/s12979-024-00445-0.

References

Glenner G, Wong C . Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun. 1984; 120(3):885-90. DOI: 10.1016/s0006-291x(84)80190-4. View

Miyakawa T, Uehara Y . Observations of amyloid angiopathy and senile plaques by the scanning electron microscope. Acta Neuropathol. 1979; 48(2):153-6. DOI: 10.1007/BF00691158. View

Fogelman A, Elahi F, Sykes K, Van Lenten B, Territo M, Berliner J . Modification of the Recalde method for the isolation of human monocytes. J Lipid Res. 1988; 29(9):1243-7. View

Haga S, Akai K, Ishii T . Demonstration of microglial cells in and around senile (neuritic) plaques in the Alzheimer brain. An immunohistochemical study using a novel monoclonal antibody. Acta Neuropathol. 1989; 77(6):569-75. DOI: 10.1007/BF00687883. View

Wisniewski H, Wegiel J, Wang K, Kujawa M, Lach B . Ultrastructural studies of the cells forming amyloid fibers in classical plaques. Can J Neurol Sci. 1989; 16(4 Suppl):535-42. DOI: 10.1017/s0317167100029887. View

Shaver S, Wall K, Wainman D, Gross P . Regional quantitative permeability of blood-brain barrier lesions in rats with chronic renal hypertension. Brain Res. 1992; 579(1):99-106. DOI: 10.1016/0006-8993(92)90747-w. View

Perlmutter L, Scott S, Barron E, Chui H . MHC class II-positive microglia in human brain: association with Alzheimer lesions. J Neurosci Res. 1992; 33(4):549-58. DOI: 10.1002/jnr.490330407. View

Mirra S, Hart M, Terry R . Making the diagnosis of Alzheimer's disease. A primer for practicing pathologists. Arch Pathol Lab Med. 1993; 117(2):132-44. View

Saunders A, Strittmatter W, Schmechel D, Pericak-Vance M, Joo S, Rosi B . Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease. Neurology. 1993; 43(8):1467-72. DOI: 10.1212/wnl.43.8.1467. View

10.

de la Torre J, Mussivand T . Can disturbed brain microcirculation cause Alzheimer's disease?. Neurol Res. 1993; 15(3):146-53. DOI: 10.1080/01616412.1993.11740127. View

11.

Roher A, Lowenson J, Clarke S, Woods A, Cotter R, Gowing E . beta-Amyloid-(1-42) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease. Proc Natl Acad Sci U S A. 1993; 90(22):10836-40. PMC: 47873. DOI: 10.1073/pnas.90.22.10836. View

12.

Hickey W . Migration of hematogenous cells through the blood-brain barrier and the initiation of CNS inflammation. Brain Pathol. 1991; 1(2):97-105. DOI: 10.1111/j.1750-3639.1991.tb00646.x. View

13.

Gan X, Robin J, Huerta J, Braquet P, Bonavida B . Inhibition of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) secretion but not IL-6 from activated human peripheral blood monocytes by a new synthetic demethylpodophyllotoxin derivative. J Clin Immunol. 1994; 14(5):280-8. DOI: 10.1007/BF01540981. View

14.

Games D, Adams D, Alessandrini R, Barbour R, Berthelette P, Blackwell C . Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein. Nature. 1995; 373(6514):523-7. DOI: 10.1038/373523a0. View

15.

Sievers J, Parwaresch R, Wottge H . Blood monocytes and spleen macrophages differentiate into microglia-like cells on monolayers of astrocytes: morphology. Glia. 1994; 12(4):245-58. DOI: 10.1002/glia.440120402. View

16.

Seebach J, Bartholdi D, Frei K, Spanaus K, Ferrero E, Widmer U . Experimental Listeria meningoencephalitis. Macrophage inflammatory protein-1 alpha and -2 are produced intrathecally and mediate chemotactic activity in cerebrospinal fluid of infected mice. J Immunol. 1995; 155(9):4367-75. View

17.

Giulian D, Li J, Bartel S, Broker J, Li X, Kirkpatrick J . Cell surface morphology identifies microglia as a distinct class of mononuclear phagocyte. J Neurosci. 1995; 15(11):7712-26. PMC: 6578049. View

18.

Mackenzie I, Hao C, Munoz D . Role of microglia in senile plaque formation. Neurobiol Aging. 1995; 16(5):797-804. DOI: 10.1016/0197-4580(95)00092-s. View

19.

Nottet H, Persidsky Y, Sasseville V, Nukuna A, Bock P, Zhai Q . Mechanisms for the transendothelial migration of HIV-1-infected monocytes into brain. J Immunol. 1996; 156(3):1284-95. View

20.

Schmidtmayerova H, Nottet H, Nuovo G, Raabe T, Flanagan C, Dubrovsky L . Human immunodeficiency virus type 1 infection alters chemokine beta peptide expression in human monocytes: implications for recruitment of leukocytes into brain and lymph nodes. Proc Natl Acad Sci U S A. 1996; 93(2):700-4. PMC: 40116. DOI: 10.1073/pnas.93.2.700. View