Imported News – Page 32

July 20, 2026

Protein Protects Against Tau Tangles, Synaptic Loss in Mouse Model of Tauopathy

Alzheimer’s disease (AD) and many other forms of neurodegeneration share a common culprit. In these diseases, tau proteins that normally stabilize neuronal microtubule filaments within nervous system networks instead form noxious knots and gradually disrupt the circuits they would otherwise preserve.

Scientists at Sanford Burnham Prebys have now shown that a different protein known as SORLA offers protection against the effects of these lethal loops. The results of the researcher’s’ study in mice suggests that future research may yield new treatments capable of boosting this protein’s ability to defend the brain.

Timothy Huang, PhD, assistant professor in the Center for Neurologic Diseases at Sanford Burnham Prebys, is senior and corresponding author of the team’s published paper in Science Advances, titled “SORLA up-regulation suppresses pathological effects in aged tauopathy mouse brain,” in which they concluded “These findings reveal a protective role for SORLA in multiple aspects of tauopathy pathogenesis and highlight its potential as a therapeutic target.”

Normally, tau proteins are found throughout the brain and nervous system, helping to maintain the shape and structure of our neuronal wiring. But in certain diseases, including Alzheimer’s disease, tau proteins clump together inside nerve cells, forming what are known as tau tangles. These toxic tangles are linked to cognitive impairment and nerve cell death in diseases known as tauopathies. “In AD, amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs) comprising hyperphosphorylated tau accumulate in brain,” the authors explained.

The new study focused on the safeguarding capabilities of protein known as SORLA. “A role for the trafficking receptor SORLA (Sortilin-related receptor containing LDLR class A repeats) in reducing Aβ levels has been well established,” the investigators continued. “… however, relatively little is known with respect to whether and how SORLA can potentially affect tau pathology in vivo.”

Timothy Huang added, “In the last 15 or 20 years, considerable data has come out from our lab and other groups showing that SORLA can suppress one of the hallmarks of Alzheimer’s disease—amyloid-beta generation and accumulation. Very little was known, however, about whether SORLA affected the tau tangles reflected on the other side of the coin in Alzheimer’s disease.”

SORLA is expressed in both neurons and glia in mouse and human brain, the authors noted. For their newly reported study the team began by crossbreeding mice that produce extra human SORLA protein, with PS19 (P301S) mice that develop tau tangles, brain atrophy and cognitive deficits. This new mouse model enabled experiments to determine SORLA’s effects on tau protein buildup and its resulting harms.

Their studies showed that an overabundance of SORLA protein protected against a number of biological processes linked to the formation of tau tangles and progression of neurodegeneration. These include reducing the addition of too many phosphate groups to tau—known as hyperphosphorylation—and the ability of misshapen tau to serve as “seeds” that attract more tau and form clumps. This protection also extended to preservation of the synapses at the junction between neurons and the brain’s ability to adjust these connection points—which is called synaptic plasticity. “Using complementary approaches, we show that SORLA overexpression attenuates ventricular enlargement, tau phosphorylation and seeding, synaptic loss, impaired synaptic plasticity, and glial hyperactivation in the PS19 mouse brains,” the team wrote in summary.

An overabundance of SORLA protein protects against a number of biological processes linked to the formation of tau tangles and progression of neurodegeneration. These include reducing the addition of too many phosphate groups to tau, known as hyperphosphorylation. In these biopsy images, less phosphorylated tau—stained to appear green—has accumulated in the bottom sample overexpressing SORLA. [Tim Huang, Huijie Huang, Sanford Burnham Prebys]

“When you upregulate SORLA, you can suppress the negative effects found in tauopathies,” said first author Huijie Huang, PhD, a staff scientist in the Huang lab at Sanford Burnham Prebys. “We found there was less brain atrophy and less tau accumulation, which was very exciting to see.”

Because some people have mutations that disable the gene carrying the code for SORLA, Sorl1, the scientists wanted to compare the outcome of having extra SORLA to having none of it at all. Tests of mice genetically modified to lack Sorl1 told a very different story. “The opposite turned out to be true when we deleted the ability to produce SORLA proteins,” said Timothy Huang. “A lack of SORLA exacerbated the harmful effects observed in tauopathies.”

To address how extra SORLA or a lack of SORLA were either ameliorating or aggravating diseases featuring tau tangles, the research team used a combination of sequencing techniques capturing the levels of all proteins and gene expression in each cell, as well as mapping the spatial relationship of RNA and proteins within brain tissue. The scientists found that upregulated SORLA prevented problematic protein production changes in the synapses between neurons while also suppressing other drivers of tauopathy disease progression. They also observed that extra SORLA tamped down on disease-related gene expression patterns in brain cells known as glial cells that support and protect neurons in many ways. “One particularly notable finding that we can build on is the upregulation of a member of the plexin-B family of receptors in the absence of SORLA,” said Huijie Huang.

“There are unique drugs that can target this class of receptors that we may be able to apply to tau-related dementia disorders,” suggested Tim Huang. “One potential future direction is to repurpose these drugs to target overactivation of glial cells and perhaps reverse some of the phenotypes in tauopathies.”

The scientists also want to better understand what happens in each individual cell type when they upregulate or downregulate SORLA. “While it is not possible to specifically determine how cell-specific modulation of SORLA can affect tau using the global transgenic overexpression/deletion models used here, we are interested in further characterizing specific effects of SORLA on tau in neurons, and the extent of SORLA modulation on glia in influencing overall tau pathology,” they stated. The team plans to graft human neurons or glial cells into the mouse brain to study the effects of different SORLA mutations.

“Mouse cells and human cells are different,” said Tim Huang. “Because we’re looking at human disease, it’s more informative if we can observe the modulation and dysfunction of SORLA in the context of a human cell inside of a diseased brain environment.”

This continued research will reveal more knowledge about the ability of SORLA to safeguard against the toxic effects of tau tangles, and how to develop new treatments or repurpose existing therapies to benefit patients suffering from Alzheimer’s disease and other tau-related dementia disorders.

The post Protein Protects Against Tau Tangles, Synaptic Loss in Mouse Model of Tauopathy appeared first on GEN – Genetic Engineering and Biotechnology News.

July 20, 2026

Patient-Derived Tumor Organoids Show Promise for Personalizing Cancer Treatment

The development of patient-derived tumor organoids for preclinical research will undoubtedly advance precision medicine research. Now, researchers have developed a pan-cancer patient-derived organoid (PDO) platform comprising 220 PDOs from 191 patients across 15 cancer types. This advance points to an increase in the use of tumor organoids as models for evaluating and optimizing cancer treatments.

This work is published in Science Advances in the paper, “Patient-derived organoids across cancers reveal conserved tumor heterogeneity and actionable therapeutic vulnerabilities.”

The team characterized the organoids extensively, showing that they retained key characteristics of the parent tumors over extended periods and showed promise in screens to identify unrecognized treatment candidates. The organoids had similarity to their parent tumors in terms of microscopic appearance, driver DNA mutations, gene expression patterns and other features.

More specifically, the comprehensive characterization demonstrated “high fidelity to parent tumors, with 93% histopathology concordance, 80% median genomic concordance for driver mutations, and a 0.85 median gene expression correlation.” Expression profiles remained largely stable over 10 passages, ensuring reproducibility for long-term screening. And clonality analysis, the authors note, showed that 85% of dominant tumor clones were preserved, with genomic concordance directly reflecting clonal similarity.

“Essentially, these organoids appear to be very good preclinical models of the parent tumor, and are practical models because they can be used long-term,” said Andrea Sboner, PhD, associate professor of pathology and laboratory medicine, director of informatics and computational biology in the Englander Institute for Precision Medicine and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell.

The team selected a subset representing patient tumors that, based on standard clinical criteria, had been deemed ineligible for treatment with a new class of drugs—PARP inhibitors. They then tested a PARP inhibitor, talazoparib, on the organoids, and found that more than half—58%—showed substantial sensitivity, implying that the current clinical criteria are excluding patients who could benefit from such drugs. The team characterized the mutational and other features that made these organoids susceptible—offering clues to how the clinical criteria might be expanded—and identified drugs that synergistically enhance talazoparib’s effects.

“You can use these organoids as patient ‘avatars’ during clinical trials of experimental therapies, for example, to get an early picture of treatment effects and side effects,” notes Juan Miguel Mosquera, MD, a professor of pathology and laboratory medicine and director of research pathology at the Englander Institute.

The scientists also envision the future use of tumor organoid technology in selecting treatments for individual patients—growing an organoid from a sample of the patient’s tumor and then testing it rapidly with different treatment regimens.

The post Patient-Derived Tumor Organoids Show Promise for Personalizing Cancer Treatment appeared first on GEN – Genetic Engineering and Biotechnology News.

July 20, 2026

Blood Protein Panel May Help Distinguish Major Dementia Types

Diagnosing dementia is rarely straightforward, particularly early in the disease course. Alzheimer’s disease, dementia with Lewy bodies, and frontotemporal dementia can overlap clinically, while mixed pathology is common in older patients. This creates a major barrier for precision medicine: treatment selection, trial enrolment, prognosis, and patient counselling increasingly require a more biologically grounded diagnosis.

Blood biomarkers have already begun to change Alzheimer’s disease diagnostics, especially for detecting amyloid and tau pathology. But the field still lacks robust plasma tools for distinguishing Alzheimer’s disease from dementia with Lewy bodies (DLB) or frontotemporal dementia (FTD).

Proteomics across dementia cohorts

A new study, published in Nature Aging, used proximity extension assay proteomics to profile plasma proteins across international dementia cohorts. In the discovery phase, researchers analyzed more than 1,300 plasma samples, including controls and individuals across preclinical, mild cognitive impairment, and dementia stages of Alzheimer’s disease, dementia with Lewy bodies, and frontotemporal dementia.

The analysis identified more than 200 dysregulated proteins across disease groups. For Alzheimer’s disease, glial fibrillary acidic protein, or GFAP, showed the strongest increase across the disease continuum. Neurofilament light chain also rose with clinical stage, while several other proteins declined as Alzheimer’s disease progressed. However, the authors emphasize that these proteomic markers did not outperform established plasma markers of amyloid and tau pathology for detecting Alzheimer’s disease.

The more clinically novel findings came from the non-Alzheimer’s dementias. In dementia with Lewy bodies, integrin alpha-V and integrin alpha-M were consistently reduced, including in analyses stratified by amyloid status and in autopsy-confirmed Lewy body disease. The same integrin-related signal was also seen in Parkinson’s disease data from the PPMI cohort, supporting a broader link to Lewy body pathology.

For frontotemporal dementia, neurofilament light chain remained one of the strongest markers, consistent with its role as a general marker of neuroaxonal injury. Lower GFAP helped distinguish frontotemporal dementia from Alzheimer’s disease, while proteins such as OSM appeared more relevant in earlier frontotemporal degeneration.

A 21-protein dementia panel

The researchers then refined these signals into a custom 21-protein plasma panel and tested it in an independent multicenter cohort. The panel showed its strongest value in differential diagnosis, helping separate dementia with Lewy bodies and frontotemporal dementia from both controls and Alzheimer’s disease dementia. Its performance was moderate to good across these comparisons, suggesting that plasma proteomics may be most useful as an added layer of biological stratification when clinical symptoms overlap.

These values are not sufficient to replace specialist clinical assessment, CSF testing, imaging, or established Alzheimer’s blood biomarkers. But they suggest that plasma proteomics could provide clinically useful support where diagnostic uncertainty remains high.

Toward biomarker-based dementia stratification

The immediate relevance is not simply another biomarker list. The study addresses a practical gap in dementia medicine: identifying scalable blood-based tools that help separate biologically different diseases with overlapping symptoms. That could improve referral pathways, enrich clinical trials with the right patient populations, and support future disease-modifying therapies beyond Alzheimer’s disease.

Important limitations remain. Many DLB and FTD diagnoses were clinical rather than autopsy-confirmed, prodromal groups were relatively small, and biomarker performance may depend on assay platform and cohort calibration. Mixed pathology, especially coexisting Alzheimer’s and Lewy body disease, remains a major challenge.

Even so, the study provides a strong proof of concept. Plasma proteomics may help move dementia diagnostics from broad syndromic categories toward molecular stratification, an essential step if precision neurology is to match the progress already seen in Alzheimer’s biomarker development.

The post Blood Protein Panel May Help Distinguish Major Dementia Types appeared first on Inside Precision Medicine.

July 20, 2026

China’s AI models have Trump’s AI world at war with itself

This story originally appeared in The Algorithm, our weekly newsletter on AI. To get stories like this in your inbox first, sign up here.

Over the weekend, several current and former advisors to President Donald Trump on AI publicly lobbed insults at the country’s leading AI companies. David Sacks, the president’s AI and crypto “czar” until March, branded Anthropic’s models as “lobotomized” and “woke.” Emil Michael, a top Pentagon official, called OpenAI’s new head of strategic futures a “supreme village idiot.”

It began because no one can agree on what to do about Kimi, a free, open source model that Chinese AI company Moonshot launched last week. It appears to rival the intelligence of models from OpenAI and Anthropic, which are very much not free.

Kimi and other Chinese models like it pose a real problem for Trump. And they’re dividing the top AI strategists in his orbit into factions. Every time a new smart, free model from China like Kimi gets released, US companies see less reason to fork out money to access models from Anthropic or OpenAI. Given that enthusiasm for these and other AI companies is driving an outsized share of economic growth, China’s AI models create both economic and political problems for the president. They are “a threat for an administration that really doesn’t want more economic bad news,” Anton Leicht, a fellow at the Carnegie Endowment, wrote on X. They’ve already rattled US stocks.

What is Trump to do? First, consider that this is all happening just a week after New York imposed the country’s first state ban on new data centers. There is growing distrust of AI companies, and I imagine a not-insignificant share of Americans would have little sympathy for OpenAI or Anthropic as they fend off cheaper competitors, and would say it’s not the government’s job to protect their interests.

On this point, they’d see a sliver of agreement (and really just a sliver) with David Sacks, who on July 19 criticized top AI companies that “want the government to eliminate their open source competition.” He has also argued that Chinese AI models have become popular because they come with fewer restrictions on how people can use them (putting aside the built-in state censorship).

Sacks, however, is out of a job. He no longer has a formal role advising Trump, and his position that more open AI is better has been largely replaced in the administration by one that sees a larger role for government intervention. The thinking behind this view is that because AI models have gotten strong enough to pose threats to national security, the government must control how they’re used.

This position has fueled the new White House review process that aims to vet AI models’ security before they’re released. Dean Ball, a former Trump AI advisor who now works for OpenAI, criticized it over the weekend as a “de facto licensing regime for frontier AI.” Ball predicted Trump may solve his Chinese open source problem with a bit of soft power, perhaps by making US companies afraid to use models like Kimi. That drew a response from Michael, who, with Secretary of Defense Pete Hegseth, has been the agency’s main liaison with AI companies. Michael called Ball the AI industry’s “supreme village idiot,” bristling at the suggestion that the government would quietly strong-arm companies rather than, as Michael put it, go through “the democratic process not some Deep State scheme.”

Left out of the conversation has been how a model like Kimi got so good in the first place. For much of the Biden administration and even the beginning of Trump’s second administration, keeping China from getting top chips was a priority. Those export controls have loosened—Trump made the controversial decision to allow Nvidia to sell more chips to China, in exchange for the US government taking a cut—and the government has alleged that some chip smuggling has taken place. But China nonetheless has limited computing power, and it’s not clear what chips the company behind Kimi used to train the model.

It’s possible that the process involved some distillation, a practice in which AI models are trained on the outputs of existing AI models. OpenAI and Anthropic have long complained that Chinese AI companies do this, and they have requested government help to put a stop to it. In April, they got it, when the Trump administration announced a series of efforts to curb the practice.

But Kimi is out there and free, and it is nearly as good as the Anthropic model the US government deemed so powerful that it was briefly shut down because it threatened national security. The weekend’s sparring suggests many in Trump’s orbit see that as a wake-up call. But nobody can agree on what for.

July 20, 2026

Memory Shaped by Brain Remodeling During Adolescence in Mice

The human brain continues developing beyond the teenage years, with crucial changes involving decision-making and emotional regulation extending into the mid-to-late 20s. Researchers at Albert Einstein College of Medicine have identified a biological process in mice that offers new insight into how memory circuits mature during this period of brain development.

The study published in PLOS Biology titled, “Retrosplenial cortical reorganization during late adolescence introduces instability of contextual memory circuits,” found that a key memory region of the mouse brain undergoes a period of remodeling during late adolescence, causing memories formed earlier in life to become temporarily more difficult to retrieve before resurfacing with less precise detail. The findings identify a biological mechanism that may explain how access to memories changes during development.

The study focused on the retrosplenial cortex (RSP) and discovered that protective mesh-like structures, called perineuronal nets, stabilize memory circuits and unexpectedly diminish during late adolescence before rebuilding in adulthood. The changes were confined to the RSP and were not observed in the nearby hippocampus, another brain region essential for memory.

“We’ve known for years that the brain continues developing through adolescence and young adulthood,” said senior author Jelena Radulovic, MD, PhD, professor of neuroscience, psychiatry, and behavioral sciences at Einstein. “Our findings begin to explain what that developmental process looks like in one of the brain’s memory circuits and how it can influence the way earlier experiences are recalled.

Previous studies suggested that the memory circuits reached maturity during early adolescence. Instead, results showed that an important stabilizing system temporarily weakened during late adolescence before recovering in adulthood.

The timing is notable because it corresponds to a period now recognized as one of continued brain maturation in humans. According to the National Institutes of Health, the brain continues developing and maturing into the mid-to-late 20s.

“The behavior matched the biology,” said lead author Hui Zhang, PhD, a research fellow at Einstein. “The retrosplenial cortex is responsible for older, more established memories. As its stabilizing structures declined, access to memories formed earlier in life became less reliable.”

To determine how these brain changes affected behavior, the researchers trained mice to associate a specific environment with a mild foot shock. The mice remembered the experience and froze when returned to the same chamber. Weeks later, many of the mice trained during early adolescence no longer showed that fear response, while mice trained during adulthood retained stable memories over the same period.

When the adolescent mice later experienced another test in a different environment, they once again responded to the original setting, demonstrating that the memories had become temporarily inaccessible rather than erased.

The researchers traced these changes to a decline in key structural proteins that help build and maintain perineuronal nets, along with reduced activity of growth factor, TGFβ2. When TGFβ2 activity was restored, the mice regained their ability to retrieve memories formed earlier in life.

By mid-adulthood, many of those memories resurfaced spontaneously, although they had become less precise. Rather than responding only to the original environment, the mice generalized their fear to unfamiliar settings. The researchers note that this pattern resembles the “reminiscence bump,” a well-known phenomenon in which adults disproportionately recall memories from adolescence and early adulthood while often remembering the emotional significance of an experience more readily than its specific details.

The findings may also have implications beyond memory. Schizophrenia and major depression often emerge in humans during late adolescence. The authors suggest that changes in this developmental process could contribute to vulnerability to psychiatric disorders in genetically susceptible individuals. Additional research is needed to evaluate whether similar mechanisms occur in humans.

The post Memory Shaped by Brain Remodeling During Adolescence in Mice appeared first on GEN – Genetic Engineering and Biotechnology News.

July 20, 2026

<![CDATA[New data show APOE4 worsens early sleep disruption in Alzheimer models; CN-105 and zolpidem restore deep sleep and may slow amyloid buildup.]]>

July 20, 2026

New CVD Risk Tool Boosts Women’s Risk, Lowers Risk for Some Black Adults

A change in the guidelines used to judge a person’s cardiovascular risk in the U.S. means who is classed as ‘at risk’ or not depending on their lipid levels and other factors will change.

Men, non‑Hispanic Black adults, and current smokers are more often moved down, whereas women and people with diabetes would see their risk category upgraded with the new tool suggests research led by Allison Peng, MD, Johns Hopkins University School of Medicine, and colleagues.

The research is published in JAMA and compares risk classification with the new PREVENT-atherosclerotic cardiovascular disease (ASCVD) tool and the 2013 pooled cohort equations, which have been the standard tools for estimating 10-year atherosclerotic cardiovascular disease risk for a long time.

The team used data from the National Health and Nutrition Examination Survey, a large ongoing study that interviews and examines a sample of the U.S. population every year and focused on 24,403 adults aged 40 to 79 years who did not already have cardiovascular disease and did not have very high levels of low‑density lipoprotein (LDL) cholesterol.

For each person, the investigators estimated the chance of a heart attack or stroke in the next 10 years using both the old and new calculators, grouped them as low, borderline, intermediate, or high risk under each system, and then asked who moved up or down. They also examined whether this reshuffling would change who is advised to take cholesterol‑lowering medicines such as statins.

The new tool removes race as an input, adds more risk factors such as body mass index and markers of glycemia and kidney disease, and predicts both 10‑ and 30‑year cardiovascular risk, whereas the old tool focused on 10‑year ASCVD and treated race as Black vs. White.

The results show 22% of study participants changed risk category with the new calculator. Around 14% of all adults were placed into a lower‑risk group, while about 7% were moved up. Around 50% of the population continued to be classed as low risk, but the borderline group grew from about 13% to 18%, while the intermediate group shrank from about 25% to 20%, while the high‑risk group did not change much from about 12% to 11% with the new tool.

Key changes show women’s risk increasing and men’s decreasing, factors such as diabetes playing a bigger role in risk estimation and Black adults being generally classed as lower risk.

In the older framework, an intermediate or high risk often directly triggered a statin recommendation. With the new tool, more patients sit in the enlarged borderline group and would be offered additional tests like coronary artery calcium scoring and allowed shared decision‑making about medications and preventive treatment. Despite these shifts, the proportion of adults for whom statins would be recommended was almost unchanged at around 50% before and after.

“Overall, cardiovascular risk reclassification with the 2026…Dyslipidemia Guideline may result in opportunities for consideration of more personalized cardiovascular risk assessment with risk enhancers and coronary artery calcium scoring to guide lipid-lowering therapy and cardiovascular disease prevention,” write the authors.

In an accompanying editorial in the same journal, Philip Greenland, MD, Northwestern University Feinberg School of Medicine, and Karen Lasser, MD, Boston Medical Center, Boston University, note that despite improving risk assessments, many people who are at risk still do not get treatment or reach suggested goals for healthy cholesterol levels.

“A large percentage of U.S. adults aged 30 years or older are candidates for guideline-directed lipid lowering therapy, and many who are currently taking lipid lowering therapy are not reaching new (or previous) low density lipoprotein cholesterol goals. This is a huge public health burden for the U.S. population for a medical condition that should be highly treatable.”

They conclude: “Given the large numbers of people who would be recommended for treatment following a risk-based discussion, these reports signify a major challenge, and so far, a missed opportunity, for the U.S. health care system.”

The post New CVD Risk Tool Boosts Women’s Risk, Lowers Risk for Some Black Adults appeared first on Inside Precision Medicine.

July 20, 2026

STAT+: The next step of site-neutral, and a fiery PBM hearing

This is the online version of STAT’s weekly email newsletter Health Care Inc. Sign up here.

Hello, everyone! I’ve seen upwards of 50,000 public comments on proposed health care regulations, but the 200,000 comments (!) on the SEC’s proposal to eliminate quarterly financial reports is jaw-dropping. Yes, a lot of them seem like automated templates from interest groups, but still. Some poor soul has to sift through them. I’d like to see you try to send 200,000 comments here (please don’t): bob.herman@statnews.com.

Site-Neutral Milk Hotel

The most consequential policy in Medicare’s recent outpatient rule is the cuts to drugs that hospitals get under the 340B discount program. But the Centers for Medicare and Medicaid Services subtly doubled down on another major policy that hospitals loathe.

Continue to STAT+ to read the full story…

July 20, 2026

<![CDATA[Why DSM reforms miss psychiatry’s key flaw: weak diagnostic validity—and how evidence-based validators could reshape diagnosis, research, and care.]]>

July 20, 2026

STAT+: A most-wanted fugitive appears to have been secretly working as a biotech executive

One of Rhode Island’s most-wanted fugitives — a former doctor convicted of sexual assault but on the run for 20 years — appears to have been living a secret life as a biotech executive.

Ronald Fischer, 70, was arrested last week by federal and Rhode Island authorities after they tracked and boarded a 56-foot sailboat cruising off the coast of New Jersey. The former anesthesiologist disappeared in 2005 while on trial for first-degree sexual assault.

The boat was registered under the name Richard Graydon, an alias used by Fischer, U.S. Marshals said. That is the same name as a doctor and seasoned drug development executive hired last March by Immix Biopharma, a Los Angeles-based biotech company, as its new chief medical officer.

Continue to STAT+ to read the full story…