Immune Response at the Crossroads of Atherosclerosis and Alzheimer's Disease

Overview

Journal Front Cardiovasc Med

Specialty Cardiology & Vascular Diseases

Date 2022 Jul 25

PMID 35872901

Authors

Natalie Stahr

Elena V Galkina

Affiliations

Soon will be listed here.

Abstract

Alzheimer's disease (AD) and cardiovascular disease (CVD) are pathologies that are characterized by common signatures of vascular dysfunction and chronic inflammation that are accelerated with aging. Importantly, epidemiological studies report an independent interaction between AD and CVD and data suggest that chronic inflammation in CVD may accelerate AD development. Atherosclerosis affects most large to medium sized arteries including those supplying the cerebral circulation. Vascular dysfunction caused by atherosclerosis results in blood brain barrier breakdown, inflammation, an impaired clearance of amyloid-beta (Aβ), and finally ends with neurovascular dysfunction. Numerous data indicate that innate and adaptive immune responses shape atherogenesis and increasing evidence suggests an implication of the immune response in AD progression. Currently, mechanisms by which these two diseases are interconnected with each other are not well-defined. In this review, we discuss the recent advances in our understanding of the intertwined role of the immune response in atherosclerosis and AD and the implications of these findings for human health.

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References

Schafer S, Zernecke A . CD8 T Cells in Atherosclerosis. Cells. 2021; 10(1). PMC: 7823404. DOI: 10.3390/cells10010037. View

Unger M, Li E, Scharnagl L, Poupardin R, Altendorfer B, Mrowetz H . CD8 T-cells infiltrate Alzheimer's disease brains and regulate neuronal- and synapse-related gene expression in APP-PS1 transgenic mice. Brain Behav Immun. 2020; 89:67-86. DOI: 10.1016/j.bbi.2020.05.070. View

Gilman S, Koller M, Black R, Jenkins L, Griffith S, Fox N . Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology. 2005; 64(9):1553-62. DOI: 10.1212/01.WNL.0000159740.16984.3C. View

Marsh S, Abud E, Lakatos A, Karimzadeh A, Yeung S, Davtyan H . The adaptive immune system restrains Alzheimer's disease pathogenesis by modulating microglial function. Proc Natl Acad Sci U S A. 2016; 113(9):E1316-25. PMC: 4780638. DOI: 10.1073/pnas.1525466113. View

Relkin N . Clinical trials of intravenous immunoglobulin for Alzheimer's disease. J Clin Immunol. 2014; 34 Suppl 1:S74-9. DOI: 10.1007/s10875-014-0041-4. View

van der Valk F, Bekkering S, Kroon J, Yeang C, Van den Bossche J, van Buul J . Oxidized Phospholipids on Lipoprotein(a) Elicit Arterial Wall Inflammation and an Inflammatory Monocyte Response in Humans. Circulation. 2016; 134(8):611-24. PMC: 4995139. DOI: 10.1161/CIRCULATIONAHA.116.020838. View

Iwashyna T, Wesley Ely E, Smith D, Langa K . Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010; 304(16):1787-94. PMC: 3345288. DOI: 10.1001/jama.2010.1553. View

Oberstein T, Taha L, Spitzer P, Hellstern J, Herrmann M, Kornhuber J . Imbalance of Circulating T17 and Regulatory T Cells in Alzheimer's Disease: A Case Control Study. Front Immunol. 2018; 9:1213. PMC: 5994416. DOI: 10.3389/fimmu.2018.01213. View

Gorle N, Vandenbroucke R . Interferons: A molecular switch between damage and repair in ageing and Alzheimer's disease. Mech Ageing Dev. 2019; 183:111148. DOI: 10.1016/j.mad.2019.111148. View

10.

Drechsler M, Megens R, van Zandvoort M, Weber C, Soehnlein O . Hyperlipidemia-triggered neutrophilia promotes early atherosclerosis. Circulation. 2010; 122(18):1837-45. DOI: 10.1161/CIRCULATIONAHA.110.961714. View

11.

Baruch K, Ron-Harel N, Gal H, Deczkowska A, Shifrut E, Ndifon W . CNS-specific immunity at the choroid plexus shifts toward destructive Th2 inflammation in brain aging. Proc Natl Acad Sci U S A. 2013; 110(6):2264-9. PMC: 3568380. DOI: 10.1073/pnas.1211270110. View

12.

Itagaki S, McGeer P, Akiyama H . Presence of T-cytotoxic suppressor and leucocyte common antigen positive cells in Alzheimer's disease brain tissue. Neurosci Lett. 1988; 91(3):259-64. DOI: 10.1016/0304-3940(88)90690-8. View

13.

Cunningham C . Systemic inflammation and delirium: important co-factors in the progression of dementia. Biochem Soc Trans. 2011; 39(4):945-53. PMC: 4157218. DOI: 10.1042/BST0390945. View

14.

Sano M, Bell K, Galasko D, Galvin J, Thomas R, van Dyck C . A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease. Neurology. 2011; 77(6):556-63. PMC: 3149154. DOI: 10.1212/WNL.0b013e318228bf11. View

15.

Keren-Shaul H, Spinrad A, Weiner A, Matcovitch-Natan O, Dvir-Szternfeld R, Ulland T . A Unique Microglia Type Associated with Restricting Development of Alzheimer's Disease. Cell. 2017; 169(7):1276-1290.e17. DOI: 10.1016/j.cell.2017.05.018. View

16.

Kisler K, Nelson A, Montagne A, Zlokovic B . Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease. Nat Rev Neurosci. 2017; 18(7):419-434. PMC: 5759779. DOI: 10.1038/nrn.2017.48. View

17.

Butcher M, Galkina E . Current views on the functions of interleukin-17A-producing cells in atherosclerosis. Thromb Haemost. 2011; 106(5):787-95. PMC: 3323667. DOI: 10.1160/TH11-05-0342. View

18.

Munawara U, Catanzaro M, Xu W, Tan C, Hirokawa K, Bosco N . Hyperactivation of monocytes and macrophages in MCI patients contributes to the progression of Alzheimer's disease. Immun Ageing. 2021; 18(1):29. PMC: 8215492. DOI: 10.1186/s12979-021-00236-x. View

19.

Heppner F, Ransohoff R, Becher B . Immune attack: the role of inflammation in Alzheimer disease. Nat Rev Neurosci. 2015; 16(6):358-72. DOI: 10.1038/nrn3880. View

20.

Wyss-Coray T . Inflammation in Alzheimer disease: driving force, bystander or beneficial response?. Nat Med. 2006; 12(9):1005-15. DOI: 10.1038/nm1484. View