Exposure to World Trade Center Dust Exacerbates Cognitive Impairment in an Animal Model of Alzheimer’s

Summary: Mice exposed to dust from the WTC showed impairments in both long and short-term memory, and spatial recognition, as well as alterations to genes associated with immune-inflammatory response and blood-brain barrier dysfunction. Findings suggest first responders who were exposed to dust from the WTC experience a peripheral-brain immune inflammatory response that leads to cognitive decline.

Source: Mount Sinai Hospital

Mice exposed to World Trade Center dust exhibit a significant impairment in spatial recognition and short- and long-term memory, as well as changes in genes related to immune-inflammatory responses and blood-brain barrier disruption, according to a study conducted by researchers from the Icahn School of Medicine at Mount Sinai and published January 17 in the Journal of Alzheimer’s Disease.

The study suggests a peripheral-brain immune inflammatory “cross-talking” that may increase the likelihood of cognitive decline, identifying key steps that may be therapeutically targetable in future studies of World Trade Center first responders.

“It is imperative that we understand the risk for Alzheimer’s disease in aging first responders and other subjects exposed to Ground Zero so that we can develop preventive initiatives,” said Giulio Maria Pasinetti, MD, PhD, the Saunders Family Professor of Neurology and Program Director for the Mount Sinai Center for Molecular Integrative Neuroresilience at Icahn Mount Sinai and senior author of the paper.

The September 11, 2001, terrorist attacks on the World Trade Center led to intense fires, which produced a massive, dense cloud of toxic gases and suspended pulverized debris comprising particles of varying sizes that contained metals, polychlorinated biphenyls, and polyaromatic hydrocarbons, among other known toxins, collectively known as World Trade Center particulate matter (WTCPM).

In the years following the attack and cleanup efforts, a cluster of chronic health conditions emerged among first responders who, working at Ground Zero for prolonged time periods, were repeatedly exposed to high levels of this particulate matter.

Among the chronic health conditions, a growing body of scientific literature indicates that these first responders may have a greater incidence of mild cognitive impairment, as well as other neurological complications like changes in white matter connectivity and/or decreased hippocampal volume, which may put them at a greater risk of developing Alzheimer’s disease later in life.

“Based on epidemiological and preliminary data, we hypothesized that first responders repeatedly exposed to Ground Zero dusts in the first week post-disaster were placed at greater risk of age-related neurological conditions like Alzheimer’s disease and Alzheimer’s disease-related dementias due to changes in blood-brain barrier permeability, and/or neuro-immune interactions,” said Ruth Iban-Arias, PhD, a postdoctoral fellow in the Department of Neurology at Icahn Mount Sinai.

“Our study revealed that acute exposure to World Trade Center particulate matter may accelerate cognitive deterioration and Alzheimer’s disease-type neuropathology in mice genetically modified to develop Alzheimer’s disease. And our transcriptomic analysis strongly suggests that this exposure may trigger generalized immune inflammatory cascades which may underlie the collective pathophysiology being experienced by first responders.”

To test their hypothesis, researchers from the Center for Molecular Integrative Neuroresilience at Mount Sinai used mice genetically engineered to develop Alzheimer’s disease (5XFAD) and wild-type mice as controls.

Mice in the treatment groups were exposed to repeated intranasal instillation of WTCPM dust—which was collected at Ground Zero within 72 hours after the attacks—for three consecutive days for three weeks, reflecting the air level exposures faced by first responders at Ground Zero.

The animals were exposed to WTCPM dust with high and low doses to identify a dose-dependent response.

Y-maze assay and novel object recognition behavioral tests were performed for working memory deficits and learning and recognition memory, respectively. During the Y-maze assay, the mouse was placed at the start of a Y-shaped maze and allowed to roam freely for 10 minutes.

Generally, mice have an innate tendency to explore the environment they have not recently visited; spatial working memory impairment in this assay is defined as behavior wherein a mouse re-enters the same arm(s) repeatedly, indicating that it does not remember which arms it has already explored.

Seven days later, mice were assessed via a novel recognition test, wherein each mouse was placed in an enclosure with two objects (a salt shaker and a toy block) and given 10 minutes to investigate. Time spent with both objects was recorded.

Each mouse was removed and subsequently returned to the enclosure that contained a familiar object from the previous trial and a novel object. Cognitively intact mice display an innate tendency to spend a greater amount of time investigating the novel object rather than the familiar one.

Thus, an animal that does not remember which object it has been exposed to previously will spend similar amounts of time exploring both objects.

Both the control and 5XFAD mice exhibited a 10 percent decrease in working memory after exposure to WTCPM dust, with only the high-exposure group displaying significant impairment compared to those not exposed to the dust.

The 5XFAD mice exposed to high doses of dust and subjected to the Novel Object Recognition task showed a 16 percent and 30 percent (short- and long-term, respectively) increased preference to explore the familiar object rather than the novel when compared to no-exposure mice, depicting underlying memory alteration, evidently due to dust exposure.

The researchers also performed transcriptomic analysis (study of the complete set of RNA transcripts that are produced in the genome) in the blood and hippocampus of both sets of mice.

Exposure to WTCPM dust evoked a variety of perturbations in immune function, cell signaling, and homeostatic functioning. Interestingly, a trending increase in neutrophils, the granulocytes of the innate immune system, was also noted in the peripheral blood of WTCPM-exposed 5XFAD mice, compared to 5XFAD mice exposed to saline solution containing no dust. Overall, significant activation of pathways with an overarching theme of inflammation including acute phase response signaling were upregulated.

WTCPM dust also exacerbated the neuroinflammatory profile in the mouse brain. The researchers found significant upregulation in the expression of genes involved in blood-brain barrier.

This shows first responders and construction workers at the scene of the WTC
The study suggests a peripheral-brain immune inflammatory “cross-talking” that may increase the likelihood of cognitive decline, identifying key steps that may be therapeutically targetable in future studies of World Trade Center first responders. Image is in the public domain

These effects are indicative of a peripherally mounted innate immune response, which might synergistically spread neuroinflammation.

Results indicate that the exposure to WTCPM may have exerted peripheral immune responses, ultimately resulting in the disruption of brain endothelial tight junction proteins and leading to a permissive vascular permeability for the migration of peripheral immune modulators to the brain.

“While we should cautiously interpret the outcomes of these preclinical studies and further investigation in the clinical setting is needed, our study provides valuable information relevant to the health of first responders.

“The data opens a new horizon for investigations to further understand the impact that acute exposure to WTCPM dust has on the accelerated onset of Alzheimer’s and related dementias in first responders who are now reaching older age,” said Dr. Pasinetti.

The Mount Sinai research team is currently conducting preclinical studies that explore the interaction between mice expressing the human form of APOE4/4 (the highest genetic risk factor in late-onset Alzheimer’s disease) and exposure to WTCPM dust to examine the possible accelerated onset of Alzheimer’s disease-type phenotype.

These studies will provide the much-needed information for preventive screening and possibly interventions in first responders and other individuals who were exposed to the dust who have genetic susceptibility to Alzheimer’s disease.

About this Alzheimer’s disease research news

Author: Elizabeth Dowling
Source: Mount Sinai Hospital
Contact: Elizabeth Dowling – Mount Sinai Hospital
Image: The image is in the public domain

Original Research: Open access.
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” by Giulio Maria Pasinetti et al. Journal of Alzheimer’s Disease


Abstract

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

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.

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  1. Thank you for your interesting article on the emerging science on the effects of WTCPM on First Responders’ cognitive health. It seems the very sad day of 9/11 will be with us for sometime to come, with developments such as this gaining coverage.

    I am writing today to clarify with you a point of great importance. In your article, paragraph 3, Your statement:

    “The September 11, 2001, terrorist attacks on the World Trade Center led to intense fires, which produced a massive, dense cloud of toxic gases and suspended pulverized debris comprising particles of varying sizes that contained metals, polychlorinated biphenyls, and polyaromatic hydrocarbons, among other known toxins, collectively known as World Trade Center particulate matter (WTCPM).”

    As a member and supporter of the research and educational organization, Architects and Engineers for 9/11 Truth, a 501 c 3 non-profit founded in 2006 by Architect RIchard Gage (https://www.ae911truth.org/), for the last 17 years, they have proven, though not yet in a court of law (due to cases being rejected by the courts due to lack of standing) and have established, as fact, that the 3 WTC Towers that fell on 9/11 were brought down with pre-set explosives and incendiaries, specifically, nano-thermite controlled-demolitions. Tower 2, the 110 story South Tower, was first to fall on 9/11, making it the first ever steel-framed high-rise to collapse due to fire, according to the ‘official narrative’. Tower 1, the 110 story North Tower, fell a few minutes later as the second ever steel-framed high-rise to fall due to fire. The 47 story Building 7, the Solomon Brothers Building, and site of the OEM headquarters for the City of New York, as well as the largest office for the CIA outside of Langley, VA, FBI, SEC and other federal offices, fell at 5:20pm in a classic implosive controlled demolition, after several loud and concussive explosions that can be heard on live news reports from that day. Normal office fires were blamed for the total collapse by the National Institute of Standards and Technology (NIST) Final Report. Several legal challenges have been made against NIST. These cases are ongoing.

    Back to the Dust:

    In fact, four dust samples were analyzed by an international team of interdisciplinary researchers from areas of study including physics, chemistry and demolition engineering who determined that active nano-thermitic sol gel residue occurred throughout the dust, exhibited highly energetic reactions when heated to 430 degrees C, produced the distinctive iron-rich spheriols observed throughout the dust samples, had very steep energetic signatures when compared to other known explosives, and display under electron microscope the intimate nesting of aluminum and iron oxide – the ingredients of thermite which is the incendiary capable of almost instantaneously melting high-grade steel.. (https://benthamopen.com/contents/pdf/TOCPJ/TOCPJ-2-7.pdf);
    image.png

    The very serious and sad aspect of your article is that though we are gaining insight into First Responders’ illnesses, the very substances causing their illnesses from the dust, were the highly engineered sol-gel nano-thermitic materials responsible for the total destruction and months of post-collapse caustic fumes and caustic gases escaping from the pile in the subfloors of the debris pile. Author and Researcher Kevin Ryan has written extensively on this topic at https://digwithin.net/2020/02/09/carbon-nanotubes/

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