A new research paper was published on the cover of Aging (listed as "Aging (Albany NY)" by Medline/PubMed and "Aging-US" by Web of Science) Volume 15, Issue 3, entitled, “Immune-mediated platelet depletion augments Alzheimer’s disease neuropathological hallmarks in APP-PS1 mice.”

In Alzheimer’s disease (AD), platelets become dysfunctional and might contribute to amyloid beta deposition. In a recent study, researchers Diana M. Bessa de Sousa, Ariane Benedetti, Barbara Altendorfer, Heike Mrowetz, Michael S. Unger, Katharina Schallmoser, Ludwig Aigner, and Kathrin Maria Kniewallner from Paracelsus Medical University and Austrian Cluster for Tissue Regeneration in Austria depleted platelets in one-year-old APP Swedish PS1 dE9 (APP-PS1) transgenic mice for five days, using intraperitoneal injections of an anti-CD42b antibody, and assessed changes in cerebral amyloidosis, plaque-associated neuritic dystrophy and gliosis. 

“The potential role of platelets in amyloid beta deposition led to the hypothesis that reducing platelet numbers might ameliorate AD pathology [30]. Here, we performed immune-mediated platelet depletion in APP-PS1 mice with an already fully developed amyloidosis and investigated its effects on classical hallmarks of AD: amyloid plaque pathology, plaque-associated neuritic dystrophy and gliosis.”

In APP-PS1 female mice, platelet depletion shifted amyloid plaque size distribution towards bigger plaques and increased neuritic dystrophy in the hippocampus. In platelet-depleted females, plaque-associated Iba1+ microglia had lower amounts of fibrillar amyloid beta cargo and GFAP+ astrocytic processes showed a higher overlap with thioflavin S+ amyloid plaques. In contrast to the popular hypothesis that platelets foster plaque pathology, data from this study suggest that platelets might limit plaque growth and attenuate plaque-related neuritic dystrophy at advanced stages of amyloid plaque pathology in APP-PS1 female mice. Whether the changes in amyloid plaque pathology are due to a direct effect on amyloid beta deposition or are a consequence of altered glial function needs to be further elucidated.

“In APP-PS1 females, acute thrombocytopenia aggravates AD neuropathology, suggesting that platelets might have a protective function in AD. However, the underlying molecular mechanisms by which platelets modulate amyloid plaque deposition remain elusive and need to be investigated in future experiments.”


DOI: https://doi.org/10.18632/aging.204502

Corresponding Author: Kathrin Maria Kniewallner - kathrin.drerup@pmu.ac.at 

Keywords: Alzheimer’s disease, platelets, amyloid-beta, microglia, astrocytes

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About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

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Aging (Aging-US)

Immune-mediated Platelet Depletion Augments Alzheimer’s Disease in Mice

Synopsis: 
Ivana Magovčević-Liebisch, PhD, JD, is the President and CEO of Vigil Neuroscience, a microglia-focused company dedicated to improving the lives of patients, caregivers, and families affected by rare and common neurodegenerative diseases by restoring the vigilance of microglia, the sentinel cells of the brain’s immune system. Ivana shares how sitting on boards of other companies has informed how she operates as CEO at Vigil. She talks about how she’s seen her role evolve as the company has grown over the last three years. She discusses the importance of having diversity and diversity of thought on the leadership team. She provides her perspective on neurology as a therapeutic area, where unmet needs still exist, and the challenges and opportunities in precision-based neurology. Finally, she shares her approach to building culture at Vigil.

Biography: 
Ivana is an accomplished pharmaceutical and biotechnology executive focused on corporate excellence and execution. She has over 20 years of senior management experience in financing, strategic partnerships, M&A, clinical development, regulatory affairs, commercialization, legal and IP strategies, and preparation and execution of operating plans. Prior to Vigil, Ivana was Executive Vice President (EVP) and Chief Business Officer at Ipsen where she was responsible for fueling the pipeline through external innovation and led the External Innovation, Business Development and Alliance Management functions. Prior to Ipsen, Ivana was EVP, Chief Strategy and Corporate Development Officer at Axcella Health, Senior VP (SVP) and Head of Global Business Development for the specialty drug business at Teva Pharmaceutical Industries Ltd. She previously worked at Dyax Corp in management roles including EVP and Chief Operating Officer where she launched the company’s first drug, Kalbitor® for an orphan indication, Hereditary Angioedema, and at Transkaryotic Therapies, Inc. Ivana serves as a member of the Board of Directors for Aeglea BioTherapeutics, Inc. Ivana holds a PhD in Genetics from Harvard University and received her JD in High Technology law from Suffolk University Law School.

Harnessing the power of microglia, Ivana Magovčević-Liebisch, President & CEO, Vigil Neuroscience

BUFFALO, NY — June 3, 2025 — A new #research paper was #published in  Aging (Aging-US) on May 1, 2025, as the #cover of Volume 17, Issue 5, titled “Defining the hypoxic thresholds that trigger blood-brain barrier disruption: the effect of age.”

In this study, researchers Arjun Sapkota, Sebok K. Halder, and Richard Milner from San Diego Biomedical Research Institute investigated how aging affects the brain’s vulnerability to low oxygen, or hypoxia. Using C57BL/6J mice ranging from 2 to 23 months of age, they identified specific oxygen levels that disrupt the blood-brain barrier (BBB)—a critical structure that protects brain tissue from harmful substances. The findings are important for understanding age-related cognitive decline and the potential risks faced by individuals with chronic oxygen-limiting conditions such as asthma, sleep apnea, emphysema, and heart disease.

The BBB is essential for maintaining brain health. In this study, mild and prolonged hypoxia—called chronic mild hypoxia—was found to compromise the BBB in mice. Older mice showed significantly more BBB disruption than younger ones. Notably, barrier weakening and blood vessel changes occurred at oxygen levels of just 15% in aged mice, compared to 13% in young mice. These data suggest that the aging brain is more sensitive to oxygen deprivation, even at levels that may be considered only mildly hypoxic.

The researchers also determined when this vulnerability emerged. The BBB showed increased sensitivity to low oxygen not only in aged mice but also in mice as young as 2 to 6 months, with a second spike occurring between 12 and 15 months—equivalent to middle age in mice. These findings may reflect age-dependent changes in brain vascular function and remodeling capacity.

“Hypoxia-induced endothelial proliferation was relatively constant across the age range, but advanced age strongly enhanced the degree of BBB disruption (4-6-fold greater in 23 months vs. 2 months old).”

Another key focus was microglial activation, a sign of brain inflammation. Aged mice exhibited higher microglial activation across all oxygen levels, including normal conditions. Chronic microglial activation is closely linked to neuroinflammation and has been implicated in diseases such as Alzheimer’s. While the rate of blood vessel formation was constant across ages, the degree of BBB disruption increased sharply with age, suggesting that repair mechanisms may weaken over time.

These results may help explain why older adults with chronic hypoxia-related diseases are at higher risk for neurodegeneration and cognitive decline. The study also draws attention to the risks of high-altitude exposure for aging populations, where oxygen levels naturally drop.

Altogether, these findings underscore the importance of protecting brain health in older individuals by managing oxygen exposure and reducing hypoxia-related risks. The researchers emphasize the need to develop new therapies that support blood-brain barrier integrity, particularly in aging populations exposed to chronic or intermittent low-oxygen conditions.

DOI - https://doi.org/10.18632/aging.206241

Corresponding author - Richard Milner - rmilner@sdbri.org

Video short - https://www.youtube.com/watch?v=Nr6rTm7aJRo

Keywords - aging, blood-brain barrier integrity, endothelial, proliferation, microglia, chronic mild hypoxia, hypoxic threshold

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Aging Increases Brain’s Sensitivity to Hypoxia and Blood-Brain Barrier Damage in Mice

First Published in Masticadores [Taiwan] in June 2025

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The Little Organoid That Could

As we age, our brains become more sensitive to stress and disease. A recent study sheds light on a lesser-known risk: reduced oxygen levels. The study, titled “Defining the hypoxic thresholds that trigger blood-brain barrier disruption: the effect of age” and recently published as the cover for Volume 17, Issue 5 of Aging (Aging-US), found that low oxygen—also called hypoxia—can harm the aging brain by disrupting the blood-brain barrier (BBB). This damage may contribute to cognitive decline, memory problems, and an increased risk of dementia.

Understanding Hypoxia in the Brain

The brain relies on a steady supply of oxygen to stay healthy. When oxygen levels fall—a condition known as hypoxia—the brain undergoes changes to adapt. These changes include the remodeling of blood vessels and, importantly, a weakening of the blood-brain barrier. The BBB acts as a filter, protecting brain tissue from harmful substances. When it breaks down, it can lead to inflammation, brain cell damage, and cognitive issues.

Hypoxia is common in older adults, especially those with conditions like sleep apnea, chronic obstructive pulmonary disease (COPD), heart failure, and asthma. That is why understanding the connection between low oxygen and the aging brain is crucial for preventing long-term neurological damage.

Full blog - https://aging-us.org/2025/06/oxygen-deprivation-and-the-aging-brain-a-hidden-trigger-for-cognitive-decline/

Paper DOI - https://doi.org/10.18632/aging.206241

Corresponding author - Richard Milner - rmilner@sdbri.org

Video short - https://www.youtube.com/watch?v=Nr6rTm7aJRo

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Keywords - aging, blood-brain barrier integrity, endothelial, proliferation, microglia, chronic mild hypoxia, hypoxic threshold

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Oxygen Deprivation and the Aging Brain: A Hidden Trigger for Cognitive Decline

Aging-US is dedicated to advancing our understanding of the biological mechanisms that drive aging and the development of age-related diseases. Our mission is to serve as a platform for high-quality research that uncovers the cellular, molecular, and systemic processes underlying aging, and translates these insights into strategies to extend healthspan and delay the onset of chronic disease.

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