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Prenatal origins of neurodegeneration: The role of maternal immune activation in Alzheimer's and Parkinson's pathobiology.

Prenatal origins of neurodegeneration: The role of maternal immune activation in Alzheimer's and Parkinson's pathobiology.

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Birnin Kebbi, NG · Author affiliation

Department of Human Anatomy, Faculty of Basic Medical Sciences, Federal University Birnin Kebbi, Kebbi State, Nigeria; Department of Anatomy, Faculty of Basic Medical Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria. Electronic address: kabir.shehu@fubk.edu.ng.
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Sokoto, NG · Author affiliation

Department of Human Anatomy, Faculty of Basic Medical Sciences, Federal University Birnin Kebbi, Kebbi State, Nigeria; Department of Anatomy, Faculty of Basic Medical Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria. Electronic address: kabir.shehu@fubk.edu.ng.
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Azare, NG · Author affiliation

Department of Anatomy, Faculty of Basic Medical Sciences, Federal University of Health Sciences Azare, Bauchi State, Nigeria; ARUA Centre of Excellence in Non-Communicable Diseases, University of Nairobi, Nairobi, Kenya.
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Bauchi, NG · Author affiliation

Department of Anatomy, Faculty of Basic Medical Sciences, Federal University of Health Sciences Azare, Bauchi State, Nigeria; ARUA Centre of Excellence in Non-Communicable Diseases, University of Nairobi, Nairobi, Kenya.
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Nairobi, KE · Author affiliation

Department of Anatomy, Faculty of Basic Medical Sciences, Federal University of Health Sciences Azare, Bauchi State, Nigeria; ARUA Centre of Excellence in Non-Communicable Diseases, University of Nairobi, Nairobi, Kenya.
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NG · Author affiliation · country only

Department of Human Anatomy, Faculty of Basic Medical Sciences, Novena University Ogume, Delta State, Nigeria.
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Original abstract

Recent evidence suggests that prenatal environmental factors, particularly maternal infection or maternal immune activation (MIA), may influence the progression of brain aging and lifetime risk for neurodegenerative disorders. The hypothesis is that even a short-lived inflammatory event during pregnancy may leave a lasting imprint on the developing brain and immune system of the fetus, such that aging or subsequent insults may later unmask neurodegenerative disorders. Support for this hypothesis comes largely from animal studies, where gestational inflammation has been shown to potentiate the onset of Alzheimer's and Parkinson's diseases (AD/PD), by increasing amyloid/tau pathology, reducing synaptic connections, and damaging nigrostriatal dopaminergic neurons. We review convergent mechanisms, including microglial priming, chronic cytokine excess, oxidative stress, epigenetic marks and proteostatic deficits, through which maternal immune activation may embed a latent "hit" that synergizes with aging to precipitate AD or PD. Furthermore, we appraise experimental models and available human data linking MIA to AD versus PD, noting shared and distinct pathways. Despite growing preclinical evidence, translation to human cohorts remains limited by heterogeneity in MIA exposure timing and outcome measures. An understanding of MIA's impact on neurodegeneration could suggest preventive strategies and interventions for early diagnosis and treatment.

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