Long-term Neurological Consequences of COVID-19 in Patients With Pre-existing Alzheimer’s and Parkinson’s Disease: A Comprehensive Review

SARS-CoV-2, the causative agent of COVID-19, has profound systemic effects, including significant impacts on the central nervous system (CNS). Emerging evidence suggests a potential link between SARS-CoV-2-induced neuroinflammation and the exacerbation or initiation of neurodegenerative diseases suc...

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Main Authors: Kelechi Wisdom Elechi, Ogundipe Oyepeju Nkem, Ndubuisi Timothy Chibueze, Ubalaeze Solomon Elechi, Kenechukwu Franklin Chimaobi
Format: Article
Language:English
Published: SAGE Publishing 2025-05-01
Series:Neuroscience Insights
Online Access:https://doi.org/10.1177/26331055251342755
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author Kelechi Wisdom Elechi
Ogundipe Oyepeju Nkem
Ndubuisi Timothy Chibueze
Ubalaeze Solomon Elechi
Kenechukwu Franklin Chimaobi
author_facet Kelechi Wisdom Elechi
Ogundipe Oyepeju Nkem
Ndubuisi Timothy Chibueze
Ubalaeze Solomon Elechi
Kenechukwu Franklin Chimaobi
author_sort Kelechi Wisdom Elechi
collection DOAJ
description SARS-CoV-2, the causative agent of COVID-19, has profound systemic effects, including significant impacts on the central nervous system (CNS). Emerging evidence suggests a potential link between SARS-CoV-2-induced neuroinflammation and the exacerbation or initiation of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). This review explores the mechanisms by which SARS-CoV-2 may contribute to neurodegenerative processes. We first discuss the pathways of viral entry into the CNS, including transneuronal and hematogenous routes, leading to blood-brain barrier (BBB) dysfunction. Neuroinflammation, mediated by the activation of microglia and astrocytes and the release of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β, is highlighted as a critical factor exacerbating neuronal damage. Oxidative stress and vascular damage are further examined as complementary mechanisms promoting neurodegeneration. In addition, we review how SARS-CoV-2 infection influences proteinopathies by accelerating the aggregation of pathological proteins like alpha-synuclein, tau, and TDP-43, contributing to disease progression in PD, AD, and related disorders. Clinical studies reporting cognitive and motor dysfunctions in post-COVID-19 patients with pre-existing neurodegenerative diseases are also summarized. Finally, this review identifies knowledge gaps and emphasizes the need for further research to clarify the long-term neurological consequences of SARS-CoV-2 infection. Understanding these mechanisms is critical for developing targeted therapeutic strategies to mitigate the risk of neurodegeneration in vulnerable populations.
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spelling doaj-art-45d681fe10bc4a42b211bca3d46ee81a2025-08-20T03:05:49ZengSAGE PublishingNeuroscience Insights2633-10552025-05-012010.1177/26331055251342755Long-term Neurological Consequences of COVID-19 in Patients With Pre-existing Alzheimer’s and Parkinson’s Disease: A Comprehensive ReviewKelechi Wisdom Elechi0Ogundipe Oyepeju Nkem1Ndubuisi Timothy Chibueze2Ubalaeze Solomon Elechi3Kenechukwu Franklin Chimaobi4Integrated Biomedical Sciences, University of Texas Health San Antonio, San Antonio, TX, USAStephen M. Ross School of Business, University of Michigan, Ann Arbor, MI, USADepartment of Microbiology, Nnamdi Azikiwe University, Awka, Anambra State, NigeriaDepartment of Radiography and Radiological Sciences, Faculty of Health Science and Technology, University of Nigeria Enugu Campus, Enugu, NigeriaDrug Delivery and Nanomedicines Research Laboratory, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Enugu State, NigeriaSARS-CoV-2, the causative agent of COVID-19, has profound systemic effects, including significant impacts on the central nervous system (CNS). Emerging evidence suggests a potential link between SARS-CoV-2-induced neuroinflammation and the exacerbation or initiation of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). This review explores the mechanisms by which SARS-CoV-2 may contribute to neurodegenerative processes. We first discuss the pathways of viral entry into the CNS, including transneuronal and hematogenous routes, leading to blood-brain barrier (BBB) dysfunction. Neuroinflammation, mediated by the activation of microglia and astrocytes and the release of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β, is highlighted as a critical factor exacerbating neuronal damage. Oxidative stress and vascular damage are further examined as complementary mechanisms promoting neurodegeneration. In addition, we review how SARS-CoV-2 infection influences proteinopathies by accelerating the aggregation of pathological proteins like alpha-synuclein, tau, and TDP-43, contributing to disease progression in PD, AD, and related disorders. Clinical studies reporting cognitive and motor dysfunctions in post-COVID-19 patients with pre-existing neurodegenerative diseases are also summarized. Finally, this review identifies knowledge gaps and emphasizes the need for further research to clarify the long-term neurological consequences of SARS-CoV-2 infection. Understanding these mechanisms is critical for developing targeted therapeutic strategies to mitigate the risk of neurodegeneration in vulnerable populations.https://doi.org/10.1177/26331055251342755
spellingShingle Kelechi Wisdom Elechi
Ogundipe Oyepeju Nkem
Ndubuisi Timothy Chibueze
Ubalaeze Solomon Elechi
Kenechukwu Franklin Chimaobi
Long-term Neurological Consequences of COVID-19 in Patients With Pre-existing Alzheimer’s and Parkinson’s Disease: A Comprehensive Review
Neuroscience Insights
title Long-term Neurological Consequences of COVID-19 in Patients With Pre-existing Alzheimer’s and Parkinson’s Disease: A Comprehensive Review
title_full Long-term Neurological Consequences of COVID-19 in Patients With Pre-existing Alzheimer’s and Parkinson’s Disease: A Comprehensive Review
title_fullStr Long-term Neurological Consequences of COVID-19 in Patients With Pre-existing Alzheimer’s and Parkinson’s Disease: A Comprehensive Review
title_full_unstemmed Long-term Neurological Consequences of COVID-19 in Patients With Pre-existing Alzheimer’s and Parkinson’s Disease: A Comprehensive Review
title_short Long-term Neurological Consequences of COVID-19 in Patients With Pre-existing Alzheimer’s and Parkinson’s Disease: A Comprehensive Review
title_sort long term neurological consequences of covid 19 in patients with pre existing alzheimer s and parkinson s disease a comprehensive review
url https://doi.org/10.1177/26331055251342755
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