Study Reveals Protein Structure Similarities in Alzheimer’s & Down Syndrome

The AHA! Team — Wed, 29 May 2024 08:12:33 +0000

Indiana University School of Medicine via News-Medical – More than 90% of people with Down syndrome, the most common chromosomal disorder in humans and the most frequent genetic cause of intellectual disability, are diagnosed with Alzheimer’s disease by ages 55-60. More than 90% of people with Down syndrome, are diagnosed with Alzheimer’s disease by ages 55-60. A new study recently published in Nature Structural and Molecular Biology uses leading-edge cryo-electron microscopy imaging technology to determine whether differences exist between the protein structures in those with Alzheimer’s disease and those with both Alzheimer’s disease and Down syndrome. Just like in Alzheimer’s disease, the neuropathological phenotype in those with Down syndrome and Alzheimer’s disease is characterized by the presence of amyloid β (Aβ) and by abnormal accumulation of tau protein. The structures of Aβ and tau filaments in Down syndrome have not been previously investigated, and it is unknown whether they are different from those of Alzheimer’s disease.” Ruben Vidal, PhD, the Luella McWhirter Martin Professor of Clinical Alzheimer’s Research at the Indiana University School of Medicine and lead investigator of the study Researchers studied images of Aβ and tau filaments, which occurs in individuals with Down syndrome, and compared with those seen in the most common form of Alzheimer’s disease. They found that the protein structures of Aβ and tau filaments in people with both Down syndrome and Alzheimer’s disease have similarities to those found in Alzheimer’s disease. Vidal said their findings may lead to better treatments for Alzheimer’s disease patients and individuals with Down syndrome. “This study is the first comparison at the near atomic level of Aβ and tau filaments between individuals with both Down syndrome and Alzheimer’s disease and individuals with only Alzheimer’s disease,” Vidal said. “Importantly, the study found variations in the structure of Aβ, but no substantial variation in the structure of tau filaments between individuals with Alzheimer’s disease and both Down syndrome and Alzheimer’s disease. This supports the notion of common mechanisms operating in people with sporadic Alzheimer’s disease and in people with both Down syndrome and Alzheimer’s disease. This knowledge is crucial for understanding Alzheimer’s disease in people with Down syndrome and assessing whether adults with both conditions could be included in Alzheimer’s disease clinical trials. People with Down syndrome are living longer than ever, but almost all of them are dying of Alzheimer’s disease when they get older” Vidal, also an investigator in IU School of Medicine’s Stark Neurosciences Research Institute, said the research team used cryogenic electron microscopy to get a close-up, 3D view of the structure of Aβ and tau filaments in two individuals with both Down syndrome and Alzheimer’s disease. The study revealed two novel types of Aβ filaments in the vascular compartment with structures different from those previously reported in Alzheimer’s disease. Vidal said the study’s findings show it is important to include people with both Down syndrome and Alzheimer’s disease in clinical trials targeting the Aβ or tau filaments. He said there are similarities between the mechanisms at play in amyloid aggregation, but more research is needed to determine whether the differences observed in vascular Aβ deposition are unique to those with Down syndrome. “We are thrilled that our cryo-EM imaging and 3D modeling techniques have facilitated the determination of the atomic structures of amyloid beta and tau fibrils in individuals with Down syndrome, shedding light on the connection between Down syndrome and Alzheimer’s disease,” said Wen Jiang, PhD, professor of biology at Purdue University and co-corresponding author of the study. “We are fortunate to have the Purdue Cryo-EM Facility, which provides exceptional resources and services that have made this research possible. We are grateful to the patients who donated their brains to the research and thankful to the NIH for funding our work.” Other study authors include co-corresponding author Bernardino Ghetti, Anllely Fernandez, Grace Hallinan, Kathy Newell and Holly Garringer, all from the IU School of Medicine; and Rejaul Hoq, Daoyi Li, Sakshibeedu Bharath, Frank Vago, Xiaoqi Zhang and Kadir Ozcan, all from Purdue University. This research was funded by the National Institutes of Health and the IU School of Medicine Department of Pathology and Laboratory Medicine. Source: Indiana University School of Medicine Journal reference: Fernandez, A., et al. (2024). Cryo-EM structures of amyloid-β and tau filaments in Down syndrome. Nature Structural & Molecular Biology. doi.org/10.1038/s41594-024-01252-3. To read the original article click here.

The post Study Reveals Protein Structure Similarities in Alzheimer’s & Down Syndrome appeared first on Amazing Health Advances.

Researchers Can Extend the Lifespan of Mice: Are WE Next?

AHA Publisher — Wed, 10 Jun 2020 07:00:29 +0000

Abigail Klein Leichman via Israel21c – Scientists from Israel and Kiev induce long-term decrease in metabolic rate and body temperature of warm-blooded animals for the first time. The naked mole rat never develops age-related diseases. It stays active and enjoys good bone health, reproductive success and mental acuity for its lifespan of up to 30 years. Two of many reasons for this creature’s healthy longevity are its low body temperature and slow metabolic rate. For the first time, researchers from the Institute of Gerontology in Kiev and Prof. Vadim Fraifeld’s Lab for the Biology of Aging at Ben-Gurion University of the Negev in Israel have replicated those conditions in lab mice. A naked mole rat generally lives about eight times longer than a mouse despite its similar size. The research results, published in Biogerontology, have intriguing implications for increasing longevity and decreasing major pathologies in humans as well. According to the scientists, the naked mole rat’s burrows are poorly ventilated, keeping oxygen levels are low and carbon dioxide levels high. This may cause the reduction in the naked mole rat’s body temperature by 3-4 degrees as compared to mice and slow its metabolism significantly. Subjecting laboratory mice to the same conditions – called a hypoxic-hypercapnic environment (HHE) — successfully reduced their body temperature and metabolic intensity for weeks and even months. And the mice in the HHE voluntarily consumed less food, which is one of the well-known factors in increased longevity. “Unexpectedly, the HHE accelerated skin wound healing, despite the lower energy expenditure,” the researchers also noted. “All in all, a chronic exposure to HHE offers a potential of being a lifespan-extending intervention as well as an efficient tool for treating the overweight and associated metabolic disorders.” The scientists explain that at one point in history, the Earth contained much lower levels of oxygen and higher levels of carbon dioxide. “There is still some memory in our cells of that period and therefore it should be possible in the future to induce such a state for longer periods,” they said. Moreover, they believe that HHE conditions could be used to help fight obesity, diabetes and perhaps even cancer. Secrets of Long Life The naked mole rat (Heterocephalus glaber), a rodent native to East Africa, has long been the subject of study because of its unusual healthy longevity and particularly its resistance to cancer. In 2012, Tel Aviv University evolutionary biologist Dorothee Huchon and colleagues at the Texas Health Science Center and the City College of New York determined another reason for the naked mole rat’s unusual life expectancy: very high levels of a neuro-protective protein called Neuregulin 1 (NRG-1) in its brain. Because NRG-1 is also found in the human brain, Huchon and her fellow researchers suggested that learning more about how aging and NRG-1 are related could be significant. Fraifeld studies many aspects of human aging genomics. Graduate students in his Lab for the Biology of Aging at BGU won an award for their study on “longevity genes,” genetic protective factors that some people are lucky enough to inherit. By modulating the activity of these genes in advanced age, it could be possible to combat major diseases. “Although an apparent paradox, it appears that the most effective way to delay or even to avert age-related diseases is to live longer,” Fraifeld told ISRAEL21c. Another prominent Israeli longevity researcher, Bar-Ilan University’s Haim Cohen, recently published a study showing that SIRT6, considered a longevity-related protein, is involved in regulating biological processes including aging, obesity, insulin resistance, inflammation and metabolism. His team hopes to identify therapeutic approaches that target and activate SIRT6. Ben-Gurion University researcher Debbie Toiber specializes in studying SIRT6 and DNA repair as models of age-related diseases. To read the original article click here. For more articles from Israel21c click here.

The post Researchers Can Extend the Lifespan of Mice: Are WE Next? appeared first on Amazing Health Advances.

longevity research Archives - Amazing Health Advances

Study Reveals Protein Structure Similarities in Alzheimer’s & Down Syndrome

Researchers Can Extend the Lifespan of Mice: Are WE Next?