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by claude@2026-07, 2026-07-04
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The study investigated whether intranasal infection with mouse-adapted SARS-CoV-2 (MA10) in aged 5xFAD transgenic mice and wild-type C57BL/6 controls affects Alzheimer’s disease neuropathology. Mice developed lung infection with acute viral pneumonia, while viral RNA was not detected in the CNS at 7 or 21 days post-infection and there was no overt glial activation or neuroinflammation. Alzheimer’s pathology measures showed no differences in amyloid beta plaque volume or number in MA10-infected 5xFAD mice versus uninfected controls, but bulk RNA sequencing and spatial transcriptomics identified widespread gene expression changes linked to neuronal and glial dysfunction and reduced vascular endothelial adhesion molecule expression in both genotypes. The paper’s main caveat is that it did not observe CNS viral presence or overt neuroinflammation at the tested timepoints. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia. It is characterized by cognitive decline and accumulation of amyloid beta (Aβ) plaques and neurofibrillary tangles. Accumulating evidence indicates that viral infection may worsen and/or increase development of established AD pathology. The COVID-19 pandemic has brought attention to the link between SARS-CoV-2 infection and neurologic conditions that vary in severity and duration, as well as the worsening of clinical symptoms in elderly people with dementia. To better understand potential mechanisms by which SARS-CoV-2 infection impacts AD neuropathology, aged 5xFAD and wildtype (WT) mice were intranasally infected with mouse-adapted SARS-CoV-2 (MA10). Intranasal infection of aged-matched (10-14 month) 5xFAD or wild type (WT) C57BL/6 mice with MA10 resulted in viral infection of the lungs that correlated with acute viral pneumonia characterized by lymphocyte inflammation and antiviral immune responses. Viral RNA was not detected within the central nervous system (CNS) of either WT or 5xFAD mice at days 7 or 21 post-infection (p.i.), nor were there signs of overt glial activation or neuroinflammation. There were no differences in either Aβ plaque volume or number within the brains of MA10-infected 5xFAD mice compared to uninfected 5xFAD mice. However, bulk RNA sequencing and spatial transcriptomics revealed evidence of altered expression of genes associated with neuronal and glial dysfunction, as well as reduced expression of genes encoding adhesion molecules in vascular endothelial cells. Collectively, these findings demonstrate that MA10 infection did not affect Aβ plaque size or numbers in 5xFAD mice, yet in both WT and 5xFAD mice, there were numerous down-stream effects on gene expression associated with resident CNS cell function.
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Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia. It is characterized by cognitive decline and accumulation of amyloid beta (Aβ) plaques and neurofibrillary tangles. Accumulating evidence indicates that viral infection may worsen and/or increase development of established AD pathology. The COVID-19 pandemic has brought attention to the link between SARS-CoV-2 infection and neurologic conditions that vary in severity and duration, as well as the worsening of clinical symptoms in elderly people with dementia. To better understand potential mechanisms by which SARS-CoV-2 infection impacts AD neuropathology, aged 5xFAD and wildtype (WT) mice were intranasally infected with mouse-adapted SARS-CoV-2 (MA10). Intranasal infection of aged-matched (10-14 month) 5xFAD or wild type (WT) C57BL/6 mice with MA10 resulted in viral infection of the lungs that correlated with acute viral pneumonia characterized by lymphocyte inflammation and antiviral immune responses. Viral RNA was not detected within the central nervous system (CNS) of either WT or 5xFAD mice at days 7 or 21 post-infection (p.i.), nor were there signs of overt glial activation or neuroinflammation. There were no differences in either Aβ plaque volume or number within the brains of MA10-infected 5xFAD mice compared to uninfected 5xFAD mice. However, bulk RNA sequencing and spatial transcriptomics revealed evidence of altered expression of genes associated with neuronal and glial dysfunction, as well as reduced expression of genes encoding adhesion molecules in vascular endothelial cells. Collectively, these findings demonstrate that MA10 infection did not affect Aβ plaque size or numbers in 5xFAD mice, yet in both WT and 5xFAD mice, there were numerous down-stream effects on gene expression associated with resident CNS cell function.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Funding Information
Alzheimer’s Association grant 105190 (TEL)
National Institutes of Health (NIH-NINDS) grant R35NS116835 (TEL)
National Institutes of Health (NIH-NIA) grant R01AG081599 (KNG)
National Institutes of Health (NIH-NIA) grant U54 AG054349 (KNG)
National Institutes of Health (NIH-NIAID) R01AI110700 (RSB)
National Cancer Institute (NCI) 5P30CA062203-26 (RAE)
National Institutes of Health (NIH-NIAID) U01AI180164 (DAN)
National Institutes of Health (NIH-NINDS) Training Grant T32 NS121727 (DIJ)
National Institutes of Health (NIH-AI) Training Grant 5T32 AI007319-33 (GMO)
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