%0 Journal Article %J J Alzheimers Dis %D 2023 %T Exposure to World Trade Center Dust Exacerbates Cognitive Impairment and Evokes a Central and Peripheral Pro-Inflammatory Transcriptional Profile in an Animal Model of Alzheimer's Disease. %A Iban-Arias, Ruth %A Trageser, Kyle J %A Yang, Eun-Jeong %A Griggs, Elizabeth %A Radu, Aurelian %A Naughton, Sean %A Al Rahim, Md %A Tatsunori, Oguchi %A Raval, Urdhva %A Palmieri, Joshua %A Huang, Zerlina %A Chen, Lung-Chi %A Pasinetti, Giulio Maria %K Alzheimer Disease %K Animals %K Cognitive Dysfunction %K Dust %K Mice %K Models, Animal %K September 11 Terrorist Attacks %X

BACKGROUND: The terrorist attacks on September 11, 2001, on the World Trade Center (WTC) led to intense fires and a massive dense cloud of toxic gases and suspended pulverized debris. In the subsequent years, following the attack and cleanup efforts, a cluster of chronic health conditions emerged among First Responders (FR) who were at Ground Zero for prolonged periods and were repeatedly exposed to high levels of WTC particulate matter (WTCPM). Among those are neurological complications which may increase the risk for the development of Alzheimer's disease (AD) later in life.

OBJECTIVE: We hypothesize that WTCPM dust exposure affects the immune cross-talking between the periphery and central nervous systems that may induce brain permeability ultimately promoting AD-type phenotype.

METHODS: 5XFAD and wild-type mice were intranasally administered with WTCPM dust collected at Ground Zero within 72 h after the attacks. Y-maze assay and novel object recognition behavioral tests were performed for working memory deficits and learning and recognition memory, respectively. Transcriptomic analysis in the blood and hippocampus was performed and confirmed by RT qPCR.

RESULTS: Mice exposed to WTCPM dust exhibited a significant impairment in spatial and recognition short and long-term memory. Furthermore, the transcriptomic analysis in the hippocampal formation and blood revealed significant changes in genes related to immune-inflammatory responses, and blood-brain barrier disruption.

CONCLUSION: These studies suggest a putative peripheral-brain immune inflammatory cross-talking that may potentiate cognitive decline, identifying for the first time key steps which may be therapeutically targetable in future studies in WTC FR.

%B J Alzheimers Dis %V 91 %P 779-794 %8 2023 %G eng %N 2 %R 10.3233/JAD-221046 %0 Journal Article %J J Alzheimers Dis %D 2020 %T Potential Novel Role of COVID-19 in Alzheimer's Disease and Preventative Mitigation Strategies. %A Naughton, Sean X %A Raval, Urdhva %A Pasinetti, Giulio M %K Aged %K Alzheimer Disease %K Betacoronavirus %K Coronavirus Infections %K COVID-19 %K Diabetes Mellitus, Type 2 %K Humans %K Interferon Type I %K Pandemics %K Pneumonia, Viral %K SARS-CoV-2 %K Synapses %X

There are a number of potential implications for the field of Alzheimer's disease (AD) stemming from the global spread of SARS-CoV-2. Neuroinflammation is known to be a prominent feature of neurodegeneration and plays a major role in AD pathology. Immune response and excessive inflammation in COVID-19 may also accelerate the progression of brain inflammatory neurodegeneration, and elderly individuals are more susceptible to severe outcomes after SARS-CoV-2 infection. Individuals with type 2 diabetes (T2D) are at an increased risk for AD as well as severe outcomes after SARS-CoV-2 infection. Genetic and socioeconomic factors influencing the rates of T2D, AD, and COVID-19 severity may create an exceptionally high-risk profile for certain demographics such as African Americans and Hispanic Americans. Type I interferon response plays an important role in both host response to viral infection, as well as AD pathology and may be a sensible therapeutic target in both AD and COVID-19.

%B J Alzheimers Dis %V 76 %P 21-25 %8 2020 %G eng %N 1 %1 https://www.ncbi.nlm.nih.gov/pubmed/32538855?dopt=Abstract %R 10.3233/JAD-200537