Document text
Principal Investigator: Natalie Celia Tronson
Organization: UNIVERSITY OF MICHIGAN AT ANN ARBOR
Fiscal Year: 2024
Award: $195,000
Funding agency: National Institute on Aging
PROJECT SUMMARY
More than 85 million cases of COVID-19 have been recorded in the US alone, and up to 40% of survivors
report Long-COVID symptoms including cognitive impairments. Together with evidence that inflammation
during adulthood increases risk for later cognitive decline, this raises the prospect that the COVID-19
pandemic will cause a future “second pandemic” in Alzheimer’s disease and age-related dementias. In this
project, we will identify specific mechanisms by which single stranded RNA (ssRNA) viruses (e.g., SARS-COV-
2) triggered innate immune signaling contributes to long-lasting memory impairments, exaggerated cognitive
decline during aging, and risk for dementias including Alzheimer’s disease. Our main goal is to determine the
impact of innate immune signaling as a consequence of ssRNA viruses on exaggeration of age-related
cognitive decline and risk for dementias including Alzheimer’s Disease. We will use a subchronic inflammation
protocol, established in my laboratory, together with behavioral tests of memory, protein biochemistry, and
gene expression assays to identify persistent changes in inflammatory state and neuroplasticity mechanisms
that exacerbate cognitive decline. We will use wild-type mice and APP/PS1 transgenic mice to determine
whether TLR7-induced inflammation causes acceleration of age-related cognitive decline and AD-like
pathology. Findings from this project will demonstrate how COVID-19, and other TLR7-induced inflammation
increases risk for dementia; identify sex differences in COVID-related vulnerability to cognitive decline; and
provide a basis for novel preventive strategies and treatments to reduce risk for Alzheimer’s disease and other
dementias in the post-COVID-19 population.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><21+ years old><AD dementia><AD model><AD related dementia><ADRD><APP-PS1><APP/PS1><Acceleration><Adult><Adult Human><Affect><Age-associated cognitive decline><Age-associated memory impairment><Age-related cognitive decline><Aging><Agonist><Alzheimer Type Dementia><Alzheimer disease dementia><Alzheimer like pathology><Alzheimer risk factor><Alzheimer sclerosis><Alzheimer syndrome><Alzheimer's><Alzheimer's Disease><Alzheimer's and related dementias><Alzheimer's disease and related dementia><Alzheimer's disease and related disorders><Alzheimer's disease like pathology><Alzheimer's disease model><Alzheimer's disease or a related dementia><Alzheimer's disease or a related disorder><Alzheimer's disease or related dementia><Alzheimer's disease related dementia><Alzheimer's disease risk><Alzheimers Dementia><Amentia><Ammon Horn><Amyloid (Aβ) plaques><Amyloid Plaques><Behavioral><Benign senescent forgetfulness><Brain><Brain Nervous System><CNS plasticity><COVID crisis><COVID epidemic><COVID pandemic><COVID survivors><COVID-19><COVID-19 affected><COVID-19 consequence><COVID-19 crisis><COVID-19 effect><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 impact><COVID-19 impacted><COVID-19 infection survivors><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 survivors><COVID-19 virus><COVID-19 years><COVID19 virus><CV-19><Cell Communication and Signaling><Cell Signaling><Chemotactic Cytokines><CoV-2><CoV2><Cognitive Disturbance><Cognitive Impairment><Cognitive Retention Disorders><Cognitive decline><Cognitive function abnormal><Cornu Ammonis><Coronavirus Infectious Disease 2019><Data><Dementia><Differences between sexes><Differs between sexes><Disease Progression><Disturbance in cognition><Encephalon><Female><Future><Gene Expression Monitoring><Gene Expression Pattern Analysis><Gene Expression Profiling><Genotype><Goals><Hippocampus><Homolog of Drosophila TOLL><Homologous Chemotactic Cytokines><Hortega cell><Immune><Immune Cell Activation><Immune signaling><Immunes><Impaired cognition><Individual><Inflammation><Inflammatory><Injury><Intercrines><Interferon Type I><Intracellular Communication and Signaling><Knowledge><Laboratories><Lipopolysaccharides><Long COVID><Long COVID-19><Long coronavirus disease><Long coronavirus disease 2019><Long-Term Effects><Longterm Effects><Mediating><Memory><Memory Deficit><Memory Disorders><Memory Loss><Memory impairment><Mice><Mice Mammals><Microglia><Molecular Analysis><Murine><Mus><Nerve Degeneration><Neuritic Plaques><Neuroimmune><Neuroimmune Mechanisms><Neuroimmune Processes><Neuroimmunomodulation><Neuron Degeneration><Neuronal Plasticity><Pathway interactions><Persons><Play><Population><Preventative strategy><Preventative treatment><Prevention strategy><Preventive strategy><Preventive treatment><Primary Senile Degenerative Dementia><Process><Protein Biochemistry><Protein/Amino Acid Biochemistry><Protocol><Protocols documentation><RNA Viruses><Recovery><Reporting><Research><Resolution><Risk><Risk Factors><Risk Reduction><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-CoV-2 survivors><SARS-CoV2><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><SIS cytokines><Senile Plaques><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome related corona virus 2><Sex Differences><Sexual differences><Signal Transduction><Signal Transduction Systems><Signaling><Survivors><Symptoms><TLR3><TLR3 gene><TLR4><TLR4 gene><TLR7><TLR7 gene><TLR8><TLR8 gene><Testing><Time><Toll Homologue><Toll-Like Receptor 3><Toll-Like Receptor 7><Toll-Like Receptor 8><Transcript Expression Analyses><Transcript Expression Analysis><Transgenic Mice><Virus><Wild Type Mouse><Woman><Work><Wuhan coronavirus><abnormally aggregated tau protein><accelerated aging><accelerated biological age><accelerated biological aging><adult youth><adulthood><age acceleration><age associated><age associated memory decline><age correlated><age dependent><age linked><age related><age related cognitive deficit><age related cognitive impairment><age related memory dysfunction><age specific><age-induced cognitive decline><age-related decline in cognition><age-related decline in cognitive function><aging associated><aging related><alzheimer model><alzheimer risk><amyloid beta plaque><amyloid-b plaque><analyze gene expression><aβ plaques><behavior test><behavioral test><beta amyloid associated pathology><beta amyloid pathology><biological signal transduction><central nervous system plasticity><chemoattractant cytokine><chemokine><chronic COVID><chronic COVID-19><chronic novel coronavirus disease 2019><cognitive dysfunction><cognitive function><cognitive loss><cored plaque><coronavirus disease 2019><coronavirus disease 2019 consequence><coronavirus disease 2019 crisis><coronavirus disease 2019 effect><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 impact><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease 2019 virus><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19><coronavirus disease-19 global pandemic><coronavirus disease-19 impact><coronavirus disease-19 pandemic><coronavirus disease-19 virus><coronavirus infectious disease-19><cytokine><dementia risk><diffuse plaque><filamentous tau inclusion><gene expression analysis><gene expression assay><gitter cell><hCoV19><hippocampal><immune activation><injuries><long haul COVID><long haul COVID-19><long haul coronavirus disease><long haul coronavirus disease 2019><long-hauler COVID><long-hauler COVID-19><long-hauler coronavirus disease 2019><long-hauler syndrome><long-term COVID><long-term COVID-19><long-term coronavirus disease><long-term coronavirus disease 2019><longterm COVID><longterm COVID-19><longterm coronavirus disease><longterm coronavirus disease 2019><male><memory decline><memory dysfunction><mesoglia><microglial cell><microgliocyte><microtubule associated protein tau aggregation><microtubule associated protein tau deposit><mid life><mid-life><middle age><middle aged><midlife><mouse model><murine model><nCoV2><neural degeneration><neural inflammation><neural plasticity><neurodegeneration><neurodegenerative><neuroinflammation><neuroinflammatory><neurological degeneration><neuronal degeneration><neuroplastic><neuroplasticity><novel><paired helical filament of tau><pandemic><pandemic disease><pathway><perivascular glial cell><persistent COVID-19><post COVID syndrome><post COVID-19 syndrome><post acute COVID syndrome><post acute COVID-19><post acute COVID-19 syndrome><post acute SARS-CoV-2><post acute coronavirus disease 2019><post acute coronavirus disease 2019 syndrome><post acute coronavirus disease syndrome><post acute severe acute respiratory syndrome coronavirus 2><post coronavirus disease 2019 syndrome><post coronavirus disease syndrome><post-COVID><post-COVID-19><post-acute phases of COVID-19><post-coronavirus disease 2019><primary degenerative dementia><prolonged COVID-19 symptoms><reduce risk><reduce risks><reduce that risk><reduce the risk><reduce these risks><reduces risk><reduces the risk><reducing risk><reducing the risk><resolutions><risk factor for dementia><risk for dementia><risk-reducing><self-aggregate tau><senile dementia of the Alzheimer type><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><sex><sex based differences><sex-dependent differences><sex-related differences><sex-specific differences><social role><survive COVID-19><survive SARS-CoV-2><tau PHF><tau accumulation><tau aggregate><tau aggregation><tau fibrillization><tau filament><tau neurofibrillary tangle><tau oligomer><tau paired helical filament><tau polymerization><tau-tau interaction><toll-like receptor 4><transcriptional profiling><wildtype mouse><young adult><young adulthood><β-amyloid pathology><τ aggregation>