Neuroinflammatory Responses Occur in Brain Lesions During Alzheimer’s Disease: Postmortem Case Report

Article type: Research Article

Authors: Belkhelfa, Mourad^{a; *} | Bekrar, Samy^a | Rezaig, Lina^a | Beder, Narimene^a | Touri, Faiza^b | Yousfi, Yamina^c | Nabi, Hedia^d | Slimani, Assia^d | Attal, Nabila^e | Belarbi, Ayed^c | Bessaha, Madjid^b | Touil-Boukoffa, Chafia^a

Affiliations: [a] Cytokines and NO-Synthases, Immunity and Pathogenesis Team, Laboratory of Cellular and Molecular Biology, Faculty of Biological Science, University of Sciences and Technology Houari Boumediene, Algiers, Algeria | [b] Department of Forensic Medicine, Issad Hassani Hospital/Algiers 1 University, Algiers, Algeria | [c] Department of Anatomopathology, Djillali Bounaama hospital/Saad Dahlab University, Blida, Algeria | [d] Department of Anatomopathology, Beni Messous Hospital/Algiers 1 University, Algiers, Algeria | [e] Pasteur institute/Algiers 1 University, Algiers, Algeria

Correspondence: [*] Correspondence to: Mourad Belkhelfa, Cytokines and NO-Synthases, Immunity and Pathogenesis Team, Laboratory of Cellular and Molecular Biology, Faculty of Biological Science, University of Sciences and Technology Houari Boumediene, Algiers, Algeria. Tel.: (+213) 558539932; E-mail: mourad.belkhelfa@gmail.com.

Abstract: Background:Alzheimer’s disease (AD) is a progressive and irreversible neurodegenerative disorder. It is characterized by a gradual decrease in cognitive function and is considered a disorder in which the intensifying neuronal loss. The autopsy is considered the gold standard for the diagnosis of AD and non-AD dementia. Objective:Our study aims to clarify the involvement of neuroinflammation processes in brain lesions of AD. Methods:The defunct was admitted to the forensic medicine department of Issad Hassani Hospital (Algeria). In order to recover the brain, an autopsy was performed within 24 hours of death and then immediately fixed in formaldehyde to maintain structural brain integrity for histological and immunohistochemical analysis. Results:Our findings indicate the presence of tissue lesions in the specific brain regions: right middle frontal gyrus, right cingulate gyrus, right putamen and globus pallidus, right caudate nucleus, right hippocampus, inferior parietal lobule, left parahippocampal gyrus, and left hippocampus. Notably, there is a predominant occurrence of lesions: granulovacuolar degeneration, Hirano bodies, cotton-wool, and neuritic plaques. The causes of neurodegenerative processes are probably related to TNF-α, IL-1β, and TGF-β production and iNOS expression by the NF-κB activation pathway in the R-HP, inducing necroptosis. Conclusions:The occurrence of neuroinflammatory responses is linked to tissue lesions in AD. The production of inflammatory cytokines is the basis of this process, which ultimately leads to the necroptosis, which is triggered by neuroinflammation amplification. The inhibition of neuroinflammation by targeting TNF-α/iNOS could stop tissue damage, this may be a promising therapeutic pathway.

Keywords: Alzheimer’s disease, brain, dementia, necroptosis, neurodegenerative disease, neuroinflammation

DOI: 10.3233/JAD-230910

Journal: Journal of Alzheimer's Disease, vol. 97, no. 3, pp. 1323-1339, 2024