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Contextualizing the Role of Osteopontin in the Inflammatory Responses of Alzheimer's Disease - PubMed

  • ️Sun Jan 01 2023

Review

Contextualizing the Role of Osteopontin in the Inflammatory Responses of Alzheimer's Disease

Roshni C Lalwani et al. Biomedicines. 2023.

Abstract

Alzheimer's disease (AD) is characterized by progressive accumulations of extracellular amyloid-beta (Aβ) aggregates from soluble oligomers to insoluble plaques and hyperphosphorylated intraneuronal tau, also from soluble oligomers to insoluble neurofibrillary tangles (NFTs). Tau and Aβ complexes spread from the entorhinal cortex of the brain to interconnected regions, where they bind pattern recognition receptors on microglia and astroglia to trigger inflammation and neurotoxicity that ultimately lead to neurodegeneration and clinical AD. Systemic inflammation is initiated by Aβ's egress into the circulation, which may be secondary to microglial activation and can confer both destructive and reparative actions. Microglial activation pathways and downstream drivers of Aβ/NFT neurotoxicity, including inflammatory regulators, are primary targets for AD therapy. Osteopontin (OPN), an inflammatory cytokine and biomarker of AD, is implicated in Aβ clearance and toxicity, microglial activation, and inflammation, and is considered to be a potential therapeutic target. Here, using the most relevant works from the literature, we review and contextualize the evidence for a central role of OPN and associated inflammation in AD.

Keywords: Alzheimer’s disease; Spp1; microglia; osteopontin.

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Conflict of interest statement

Neither Everglades BioPharma nor Integene International LLC had any role in the design of the study, collection, analyses, or interpretation of data, the writing of the manuscript, or the decision to publish.

Figures

Figure 2
Figure 2

Multifunctionality of osteopontin (OPN) and its roles in recruiting and maintaining disease-associated microglia (DAM). Elevated levels of the C-fragment of OPN in cerebrospinal fluid (CSF) mark the progression of patients with mild cognitive impairment (MCI) to clinical Alzheimer’s disease (AD). Rosmus et al., Wirths et al., Cappellano et al., Sun et al., Simonsen et al., Carecchio et al. [3,21,54,116,126,130].

Figure 3
Figure 3

Opposing roles of osteopontin (OPN) in driving Alzheimer’s disease (AD) progression (Wang (2020) [133]; Rentsendorj (2018) [95]).

Figure 4
Figure 4

Opposing roles of osteopontin (OPN) in driving Alzheimer’s disease (AD) pathology (De Schepper (2023) [121]; Quan (2021) [135]).

Figure 1
Figure 1

Hallmarks of Alzheimer’s Disease (AD), include cytoplasmic neurofibrillary tangles (NFTs) and extracellular amyloid beta (Aβ) plaques. β- and γ-secretases cleave the amyloid precursor protein (APP) into Aβ fragments that, along with hyperphosphorylated tau, generate neurotoxic aggregates and eventually insoluble plaques.

Figure 5
Figure 5

OPN positive and negative microglial subsets accumulate around pathogenic plaques in the Alzheimer’s disease (AD) brain (Qiu et al. 2023) [139].

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