Alzheimer’s disease (AD) is a chronic multifactorial and complex neuro-degenerative disorder characterized by memory impairment and loss of cognitive ability which is a plight for the elderly. AD is an aging brain pathology, and maybe it is a combination of different diseases or various symptoms that are orchestrated in common. Alzheimer’s disease is the most common type of dementia and it may contribute to 60–70% of cases. Pathologically intracellular accumulation of abnormally phosphorylated Tau protein to form neurofibrillary tangles, extracellular amyloid-beta (Aβ) deposition to form senile plaques, neural disconnection, neural deaths and synaptic dysfunction within the brain are hallmark pathologies that characterize AD. The prevalence of the disease continues to increase globally due to the increase in longevity, quality of life, and medical treatment for chronic diseases that decrease mortality and enhance the survival among elderly. Medical awareness and accurate diagnosis of the disease also contribute to the high prevalence observed globally. Unfortunately, no magic treatment exists to modify the course of AD, and no available treatment is capable to mitigate the cognitive decline or reversing the pathology of the disease yet.
A Plethora of hypothesis beginning from cholinergic to the dominant Aβ cascade hypothesis to the abnormally excessive phosphorylated Tau protein were reported. Various explanations for the pathogenesis of AD such as abnormal excitation of glutamate system and mitochondrial dysfunction were also suggested. Despite the continuous stumble to deliver significant benefits and effective treatment for this agonizing global aging illness, multiprong approaches and strategies to ameliorate the disease course are urgently needed based on the knowledge of the underpinning pathogenesis of AD.
Immunosenescence is a procedure of immune deficit that appears with age (inflammaging process) and encompasses remodeling of lymphoid organs, leading to alterations in the immune function and neuroinflammation in advanced aging, which is closely linked to the outgrowth of infections, autoimmune diseases, and malignant cancers. It is well known that long-standing inflammation influence badly the brain over the course of a lifetime due to the senescence of the immune system.
Herein, we want to trace the role of the immune system in the pathogenesis of AD, thus we are going to explore alternative avenues, such as neuroimmune involvement in the pathogenesis of AD. Determination of the initial triggers engaged in neuroinflammation, which is an early episode of the presymptomatic stages of AD and contributes to the advancement of the disease and the underlying key mechanisms of brain damage that might help the development of therapeutic strategies to combat this devastating disease. In addition, this study represents how different aspects of the immune system, both in the brain and peripherally, behave to contribute to AD.
Author(s) Details:
Abdalla Bowirrat
Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel 40700, Israel.
Aia Bowirrat M. D.
Department of Orthopedic Surgery, Hasharon Hospital, Rabin Medical Center, Petah Tikwa, Israel.
Recent Global Research Developments in Neuropathological Insights into Alzheimer’s Disease Diagnosis
- Neurobiological Advancements and Treatment Strategies: Recent studies have highlighted the intricate interactions among genetic, molecular, and environmental factors in Alzheimer’s disease (AD). Emerging treatments involve targeting multiple pathways such as inflammation, oxidative stress, and synaptic dysfunction. Clinical trials using humanized monoclonal antibodies focusing on immunotherapies to eliminate amyloid-beta have shown promise [1] .
- New Targets and Biomarkers: Researchers at Emory University have identified new targets and biomarkers for potential novel therapies. They found that amyloid beta deposits serve as a scaffold for the accumulation of other proteins, which could be the actual culprits causing brain cell damage [2] .
- Neuropathological Diagnosis: A review outlines the pathologic features of Alzheimer’s disease, including granulovacuolar degeneration and Hirano bodies, which are findings of uncertain significance [3] .
- Deep Neuropathological Phenotyping: Advances in in-vivo biomarkers and machine learning algorithms have permitted significant strides in understanding Alzheimer’s disease. These technologies pave the way for potential new therapies and precision medicine approaches [4] .
- Neurobiology and Clinical Perspectives: Significant advancements have been made in understanding Alzheimer’s disease from both neurobiological and clinical perspectives. This includes exploring the complex systems underlying AD and unveiling insights that could revolutionize therapeutic approaches [1] .
References
- Anitha K, Singh, M.K., Kohat, K. et al. Recent Insights into the Neurobiology of Alzheimer’s Disease and Advanced Treatment Strategies. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-04384-1
- In breakthrough Alzheimer’s discovery, research team finds new targets and biomarkers for potential novel therapieshttps://www.sciencedaily.com/releases/2024/08/240812123217.htm
- DeTure, M.A., Dickson, D.W. The neuropathological diagnosis of Alzheimer’s disease. Mol Neurodegeneration 14, 32 (2019). https://doi.org/10.1186/s13024-019-0333-5
- Mustafa N Shakir, Brittany N Dugger, Advances in Deep Neuropathological Phenotyping of Alzheimer Disease: Past, Present, and Future, Journal of Neuropathology & Experimental Neurology, Volume 81, Issue 1, January 2022, Pages 2–15, https://doi.org/10.1093/jnen/nlab122
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