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

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-1ß, and TGF-ß 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.

The involvement of neuroinflammation and necroptosis in the hippocampus during vascular dementia.

The prevalence of vascular dementia is increasing at an alarming rate. The Confirmation of the clinical diagnosis of vascular dementia depends on post-mortem examination of the brain. In our study, we investigated the vascular disease and neuroinflammation during vascular dementia. Our results showed a ß-amyloid deposits, neovascularization, neuronal hypertrophy and neuroinflammation in the hippocampus tissue. Interestingly, the neuroinflammation was characterized by a higher expression of TNF-α, IL-1ß, TGF-ß and iNOS which are TLR4/RelA pathway dependent. Finally, the finding of necroptosis by impaired blood supply and inflammation state suggests that the cognitive impairment was caused by vascular disease and neuroinflammation.