Connect with us

Alzheimer's

AI Helps Unravel Alzheimer’s Mystery and Identify a Therapeutic Candidate

A new study found that a gene recently recognized as a biomarker for Alzheimer’s disease is actually a cause of it, due to its previously unknown secondary function that triggers a pathway that disrupts how cells in the brain turn genes on and off.

Avatar photo

Published

on

The latest study published in Cell has revealed that phosphoglycerate dehydrogenase (PHGDH), previously known as a biomarker for early detection of Alzheimer’s disease, is actually a causal gene for spontaneous Alzheimer’s. Using artificial intelligence to visualize the three-dimensional structure of PHGDH, researchers at the University of California San Diego discovered a previously unknown regulatory role played by the protein.

The study found that altering PHGDH expression levels had consequential effects on Alzheimer’s disease progression in mice and human brain organoids. Lower levels corresponded to less disease progression, whereas increasing the levels led to more disease advancement. This established that PHGDH is indeed a causal gene for spontaneous Alzheimer’s disease.

In further support of this finding, the researchers determined that PHGDH triggers a pathway that disrupts how cells in the brain turn genes on and off, leading to issues such as the development of Alzheimer’s disease.

The research team used AI again to identify NCT-503, a small molecule with the potential to inhibit PHGDH’s regulatory role. They tested NCT-503 in two mouse models of Alzheimer’s disease and observed that it significantly alleviated Alzheimer’s progression, demonstrating substantial improvement in memory and anxiety tests.

While there are limitations to their study, the results are promising, according to lead author Sheng Zhong. “Now there is a therapeutic candidate with demonstrated efficacy that has the potential of being further developed into clinical tests,” he said.

“The next steps will be to optimize the compound and subject it to FDA IND-enabling studies.” An advantage of small molecules is that they could even be administered orally, unlike current treatments that require infusions.

Alzheimer's

The Surprising Link Between Curiosity and Healthy Aging

Psychology literature has shown that curiosity tends to decline with age. Psychologists shows one type of curiosity can increase well into old age, contradicting prior research. Older adults who maintain curiosity and want to learn new things relevant to their interests may be able to offset or even prevent Alzheimer’s disease. Conversely, those who show muted curiosity and disinterest may be at risk for dementia.

Avatar photo

Published

on

The secret to aging successfully may not be what you think. Instead of focusing on physical exercise or mental stimulation alone, research suggests that cultivating curiosity can play a significant role in maintaining cognitive health and even preventing Alzheimer’s disease. An international team of psychologists has found that older adults who maintain a curious mindset and seek out new knowledge relevant to their interests may be able to offset or prevent dementia.

This finding challenges prior research that suggested curiosity decreases with age. The study, published in the journal PLOS One, was led by UCLA psychologist Alan Castel and involved a large sample of participants between the ages of 20 and 84. The researchers aimed to tease apart two types of curiosity: trait curiosity (a general level of inquisitiveness) and state curiosity (a momentary feeling of curiosity experienced when engaging with specific topics).

To assess these forms of curiosity, the researchers asked participants to complete an online questionnaire and guess answers to hard trivia questions. Analysis showed that while trait curiosity did decline across the adult lifespan, state curiosity increased sharply after middle age and continued upward well into old age.

The study’s lead author, Mary Whatley, notes that this finding may be related to selectivity theory, which suggests that as people get older, they become more selective about what they want to learn. This aligns with research on lifelong learning, where many older adults engage in activities like taking classes or picking up hobbies.

Castel’s own work on memory has shown that people tend to quickly forget information that doesn’t engage their curiosity. Anecdotally, many older adults report that staying curious is crucial for maintaining cognitive health and preventing dementia.

This study was supported by the National Institutes of Health’s National Institute on Aging, the Leverhulme Trust, and the Alexander von Humboldt Foundation. The findings suggest that cultivating curiosity can be a key factor in healthy aging and may even help prevent or offset Alzheimer’s disease.

Continue Reading

Alzheimer's

“Unlocking Brain Resilience: Researchers Discover CLU Protein’s Potential to Protect Against Alzheimer’s Disease”

Recently approved Alzheimer’s drugs offer a step forward for treating the disease, but new therapeutic strategies are needed to complement them and provide personalized therapeutic approaches. Researchers have identified a potential strategy to protect against Alzheimer’s disease by increasing the clusterin protein (CLU).

Avatar photo

Published

on

As scientists continue to search for effective treatments for Alzheimer’s disease, a recent study has shed light on a promising new approach. Researchers at Mass General Brigham have discovered that increasing levels of the “CLU” (clusterin) protein may protect against cognitive decline and potentially provide a complementary therapy to existing treatments.

Led by Dr. Tracy Young-Pearse, the research team used various models, including human brain tissue from over 700 participants and animal models, to uncover the molecular role of CLU in protecting against neurodegeneration. Their findings suggest that increasing CLU can prevent inflammatory interactions between brain cells called astrocytes and microglia, which are associated with heightened inflammation.

The study’s results have significant implications for the design and testing of new therapeutic strategies for Alzheimer’s disease. As Dr. Young-Pearse noted, “Increasing clusterin has the potential to prevent cognitive decline in a way that is different than and complementary to anti-amyloid therapies to promote brain resilience.”

CLU may also be beneficial for treating other age-related brain diseases, many of which share similar mechanisms of neuroinflammatory dysregulation. The researchers emphasize the importance of personalized therapeutic approaches, as individuals’ responses to CLU upregulation vary based on their genetics.

The study’s findings provide a crucial step forward in the search for effective treatments for Alzheimer’s disease and other age-related brain diseases. By understanding the role of CLU in protecting against neurodegeneration, researchers can develop new strategies to promote brain resilience and potentially prevent cognitive decline.

In conclusion, the discovery of CLU’s potential therapeutic benefits offers new hope for individuals affected by Alzheimer’s disease and other age-related brain disorders. Further research is necessary to fully explore this promising approach, but the findings of this study mark an important milestone in the pursuit of effective treatments for these debilitating diseases.

Continue Reading

Alzheimer's

Physical Activity in Middle Age May Help Prevent Alzheimer’s Disease

An increase in physical activity between the ages of 45 and 65 could help prevent Alzheimer’s disease, while inactivity may be detrimental to brain health.

Avatar photo

Published

on

Physical Activity in Middle Age May Help Prevent Alzheimer’s Disease

A recent scientific study has shed light on the importance of physical activity in middle age for preventing Alzheimer’s disease. The research, published in Alzheimer’s & Dementia, highlights the need to promote physical activity among adults aged 45-65.

The study found that increasing physical activity during this period can help prevent Alzheimer’s disease, while a sedentary lifestyle may be detrimental to brain health. In fact, it is estimated that 13% of Alzheimer’s disease cases worldwide can be attributed to physical inactivity.

The World Health Organization (WHO) recommends at least 150-300 minutes of moderate activity per week or 75-150 minutes of vigorous activity per week. While extensive research has shown that exercise reduces the risk of Alzheimer’s disease by improving cardiovascular and mental health, this study suggests that physical activity may have a direct impact on the development of brain pathology associated with the disease.

The research team conducted a four-year follow-up of middle-aged residents of Catalonia with a family history of Alzheimer’s disease. Participants were classified as adherent (meeting WHO recommendations), non-adherent (doing less than the recommended amount of physical activity), and sedentary (doing zero minutes of physical activity per week).

The study found that participants who increased their physical activity to meet WHO-recommended levels showed less beta-amyloid accumulation, a protein that can impair neural communication when it accumulates in the brain. Moreover, this effect appeared to be dose-dependent; the greater the increase in activity, the greater the reduction in amyloid burden.

Non-sedentary participants also showed a greater cortical thickness in brain regions associated with Alzheimer’s disease. Cortical thickness is crucial for memory, and its thinning or atrophy (loss of volume) is an early sign of neurodegeneration.

“The findings reinforce the importance of promoting physical activity in middle age as a public health strategy for Alzheimer’s prevention,” emphasizes Eider Arenaza-Urquijo, ISGlobal researcher and lead investigator of the study. “Interventions aimed at promoting increased physical activity could be key to reducing the incidence of the disease in the future.”

Continue Reading

Trending