Top issue: Inflammatory factors can prevent Alzheimer's disease!

‍‍Alzheimer's disease (AD) is the most common, irreversible and progressive form of dementia
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The "World Report on Alzheimer's Disease 2018" shows that every 3 seconds, 1 patient with dementia occurs globally
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It is estimated that by 2050, there will be 152 million dementia patients in the world, of which about 60%-70% will be patients with Alzheimer's disease (AD)
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Alzheimer's disease was widely known as the "long farewell" in the late 20th century due to the slow deterioration of brain function and memory
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More than 100 years ago, scientist Alois Alzheimer (Alois Alzheimer) first discovered plaques in the brains of Alzheimer's patients
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Since then, one of the hallmarks of Alzheimer's disease (AD) has been the accumulation of amyloid beta plaques in the brain
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Source: medlineplus But in recent years, scientists have discovered an interesting phenomenon: some elderly people with normal cognitive abilities also found many amyloid beta plaques and tangles in their brains during imaging examinations
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Scientists are very curious about this phenomenon.
Why do some people have amyloid in their brains but their cognitive abilities are still normal, while others experience cognitive decline? To explain the reasons behind this, scientists at Massachusetts General Hospital (MGH) and Harvard Brain Aging Research (HABS) recruited 298 men and women, who were between 50 and 90 years old
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All participants took blood samples and underwent a positron emission tomography (PET) brain imaging scan
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The researchers screened nine cytokines in the blood of each participant to see if these cytokines are related to cognitive decline and the speed of brain changes
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The research was published in Alzheimer's & Dementia on June 23, 2021
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 The results of the study found that people with high levels of amyloid beta in the brain but high levels of the pro-inflammatory cytokine interleukin 12 (IL-12) have almost no cognitive decline
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However, if the IL-12 value is low, men and women with elevated amyloid levels have more cognitive decline.
At the same time, high levels of IL-12 are also associated with fewer tau tangles
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In addition, in addition to the pro-inflammatory cytokine interleukin 12 and slower cognitive decline, the pro-inflammatory cytokine interferon-γ (IFN-γ) can also delay cognitive decline
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Regardless of whether there is amyloid deposits in the brain, elevated IFN-γ levels are associated with slower cognitive decline
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 So why do high levels of interleukin-12 and interferon-γ (IFN-γ) prevent cognitive decline when there are amyloid plaques in the brain? How do IL-12 and IFN-γ prevent cognitive decline? Coincidentally, a study published in Nature on July 13 answers these two questions
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The study found that a part of astrocytes tried to release a molecule called interleukin 3 (IL-3) to transform the killer microglia into no longer destroying neurons but focusing on clearing amyloid β The sediments entangle with Tau to prevent Alzheimer's disease
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 In the brain, microglia and astrocytes are the stewards of the brain and are responsible for removing nerve debris, including plaques and tangles
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When neurons begin to die in large numbers, microglia and astrocytes are activated and cause neuroinflammation
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In a pathological state, activated microglia are the commander of the inflammatory state of brain tissue.
They will over-engulf the dendritic spines of neurons and cause a large number of neuronal deaths-the main reason for patients' cognitive decline
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In the case of Alzheimer’s disease, neuronal cell death caused by amyloid beta deposits and Tau tangles activates microglia and astrocytes, causing a neuro-inflammatory response.
Occurs, the number of neuronal deaths is at least 10 times the number of deaths caused by plaques and tangles
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And this new study on Nature shows that a part of astrocytes convert killer microglia by releasing interleukin 3 (IL-3) molecules to no longer destroy neurons, but instead focus on removing starch.
Β-like protein deposits and Tau tangles
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In this study, astrocytes constitutively produced IL-3, which triggered the transcription, morphology, and functional programming of microglia, giving them an acute immune response program and the ability to accumulate and clear Aβ and Tau aggregates
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These changes limit AD pathology and cognitive decline
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The researchers identified IL-3 as a key mediator of astrocyte-microglia crosstalk and a node for AD therapeutic intervention
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Next, the researchers further verified the role of IL-3 in a mouse model.
After removing IL-3 in the mouse model, the researchers found that the mice produced greater amyloid deposits compared to The control group also had worse memory
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When IL-3 was injected into the brain of the animal model, it was found that microglia began to gather around the amyloid deposits for cleaning, the amyloid deposits were reduced, and the animal's memory was also improved
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 In summary, the above two results indicate that because IL-3 not only helps to curb neuroinflammation, but also induces microglia to clear Aβ and Tau aggregates, IL-3 signaling may provide a new therapeutic opportunity To combat neurological diseases, such as increasing the level of IL-3 in the brain
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At the same time, IL-12 and IFN-γ may one day be measured together with other biomarkers to predict the future brain health of cognitively normal people
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References: 1.
Hyun-Sik Yang et al, Plasma IL-12/IFN-γ axis predicts cognitive trajectories in cognitively unimpaired older adults, Alzheimer's & Dementia (2021).
DOI: 10.
1002/alz.
123992.
Astrocytic interleukin-3 programs microglia and limits Alzheimer's disease, Nature (2021).
Written by | Jessica Editor | Jessica‍‍