Inflammatory Aspects of Alzheimer's Disease

Overview

Journal Acta Neuropathol

Specialty Neurology

Date 2024 Aug 28

PMID 39196440

Authors

Pablo Botella Lucena

Michael T Heneka

Affiliations

Soon will be listed here.

Abstract

Alzheimer´s disease (AD) stands out as the most common chronic neurodegenerative disorder. AD is characterized by progressive cognitive decline and memory loss, with neurodegeneration as its primary pathological feature. The role of neuroinflammation in the disease course has become a focus of intense research. While microglia, the brain's resident macrophages, have been pivotal to study central immune inflammation, recent evidence underscores the contributions of other cellular entities to the neuroinflammatory process. In this article, we review the inflammatory role of microglia and astrocytes, focusing on their interactions with AD's core pathologies, amyloid beta deposition, and tau tangle formation. Additionally, we also discuss how different modes of regulated cell death in AD may impact the chronic neuroinflammatory environment. This review aims to highlight the evolving landscape of neuroinflammatory research in AD and underscores the importance of considering multiple cellular contributors when developing new therapeutic strategies.

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References

Acosta C, Anderson H, Anderson C . Astrocyte dysfunction in Alzheimer disease. J Neurosci Res. 2017; 95(12):2430-2447. DOI: 10.1002/jnr.24075. View

Carlos Acosta J, Banito A, Wuestefeld T, Georgilis A, Janich P, Morton J . A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol. 2013; 15(8):978-90. PMC: 3732483. DOI: 10.1038/ncb2784. View

Alonso A, Grundke-Iqbal I, Iqbal K . Alzheimer's disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules. Nat Med. 1996; 2(7):783-7. DOI: 10.1038/nm0796-783. View

Asai H, Ikezu S, Tsunoda S, Medalla M, Luebke J, Haydar T . Depletion of microglia and inhibition of exosome synthesis halt tau propagation. Nat Neurosci. 2015; 18(11):1584-93. PMC: 4694577. DOI: 10.1038/nn.4132. View

Avila-Munoz E, Arias C . When astrocytes become harmful: functional and inflammatory responses that contribute to Alzheimer's disease. Ageing Res Rev. 2014; 18:29-40. DOI: 10.1016/j.arr.2014.07.004. View

Basak J, Verghese P, Yoon H, Kim J, Holtzman D . Low-density lipoprotein receptor represents an apolipoprotein E-independent pathway of Aβ uptake and degradation by astrocytes. J Biol Chem. 2012; 287(17):13959-71. PMC: 3340151. DOI: 10.1074/jbc.M111.288746. View

Basheer N, Smolek T, Hassan I, Liu F, Iqbal K, Zilka N . Does modulation of tau hyperphosphorylation represent a reasonable therapeutic strategy for Alzheimer's disease? From preclinical studies to the clinical trials. Mol Psychiatry. 2023; 28(6):2197-2214. PMC: 10611587. DOI: 10.1038/s41380-023-02113-z. View

Bateman R, Xiong C, Benzinger T, Fagan A, Goate A, Fox N . Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med. 2012; 367(9):795-804. PMC: 3474597. DOI: 10.1056/NEJMoa1202753. View

Bell R, Winkler E, Sagare A, Singh I, LaRue B, Deane R . Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron. 2010; 68(3):409-27. PMC: 3056408. DOI: 10.1016/j.neuron.2010.09.043. View

10.

Bellaver B, Povala G, Ferreira P, Ferrari-Souza J, Leffa D, Lussier F . Astrocyte reactivity influences amyloid-β effects on tau pathology in preclinical Alzheimer's disease. Nat Med. 2023; 29(7):1775-1781. PMC: 10353939. DOI: 10.1038/s41591-023-02380-x. View

11.

Bellenguez C, Kucukali F, Jansen I, Kleineidam L, Moreno-Grau S, Amin N . New insights into the genetic etiology of Alzheimer's disease and related dementias. Nat Genet. 2022; 54(4):412-436. PMC: 9005347. DOI: 10.1038/s41588-022-01024-z. View

12.

Berberich I, Shu G, Clark E . Cross-linking CD40 on B cells rapidly activates nuclear factor-kappa B. J Immunol. 1994; 153(10):4357-66. View

13.

Bettcher B, Tansey M, Dorothee G, Heneka M . Peripheral and central immune system crosstalk in Alzheimer disease - a research prospectus. Nat Rev Neurol. 2021; 17(11):689-701. PMC: 8439173. DOI: 10.1038/s41582-021-00549-x. View

14.

Bhaskar K, Konerth M, Kokiko-Cochran O, Cardona A, Ransohoff R, Lamb B . Regulation of tau pathology by the microglial fractalkine receptor. Neuron. 2010; 68(1):19-31. PMC: 2950825. DOI: 10.1016/j.neuron.2010.08.023. View

15.

Bhusal A, Afridi R, Lee W, Suk K . Bidirectional Communication Between Microglia and Astrocytes in Neuroinflammation. Curr Neuropharmacol. 2022; 21(10):2020-2029. PMC: 10556371. DOI: 10.2174/1570159X21666221129121715. View

16.

Boillee S, Yamanaka K, Lobsiger C, Copeland N, Jenkins N, Kassiotis G . Onset and progression in inherited ALS determined by motor neurons and microglia. Science. 2006; 312(5778):1389-92. DOI: 10.1126/science.1123511. View

17.

Bolos M, Llorens-Martin M, Jurado-Arjona J, Hernandez F, Rabano A, Avila J . Direct Evidence of Internalization of Tau by Microglia In Vitro and In Vivo. J Alzheimers Dis. 2015; 50(1):77-87. DOI: 10.3233/JAD-150704. View

18.

Borst K, Dumas A, Prinz M . Microglia: Immune and non-immune functions. Immunity. 2021; 54(10):2194-2208. DOI: 10.1016/j.immuni.2021.09.014. View

19.

Bouvier D, Jones E, Quesseveur G, Davoli M, Ferreira T, Quirion R . High Resolution Dissection of Reactive Glial Nets in Alzheimer's Disease. Sci Rep. 2016; 6:24544. PMC: 4835751. DOI: 10.1038/srep24544. View

20.

Brelstaff J, Mason M, Katsinelos T, McEwan W, Ghetti B, Tolkovsky A . Microglia become hypofunctional and release metalloproteases and tau seeds when phagocytosing live neurons with P301S tau aggregates. Sci Adv. 2021; 7(43):eabg4980. PMC: 8528424. DOI: 10.1126/sciadv.abg4980. View