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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.

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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.

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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.

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

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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…

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

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<![CDATA[FDA grants Fast Track to Acadia’s remlifanserin for Alzheimer disease psychosis, targeting hallucinations and delusions as RADIANT trial advances toward 2026 data.]]>
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STAT+: Pharmalittle: We’re reading about a telehealth firm and patient safety, PBMs overcharging, and more

Good morning, everyone, and welcome to another working week. We hope the weekend respite was relaxing and invigorating because that oh-too-familiar routine of meetings, deadlines, and the like has returned with a vengeance. You knew this would happen, yes? To cope, we are relying, as always, on cups of stimulation. Our choice today is laced with traces of cocoa. Feel free to join us. Remember, no prescription is required. Meanwhile, here are some tidbits to help you along. Best of luck accomplishing your goals today and, of course, do keep in touch. …

Novo Nordisk, maker of Ozempic and Wegovy, lists the telehealth company LifeMD on its website as a provider that offers “legitimate medicine sourcing and patient support” for people seeking GLP-1 drugs. But some former employees describe LifeMD differently, as a company that has sought to maximize the volume of prescriptions it doles out at the expense of patient safety, STAT reports. Former workers told STAT that providers were pressed to expedite their work to a pace that was not clinically responsible, with two of them saying providers at times were expected to review the cases of 25 people per hour based only on electronic forms the patients filled out — the equivalent of spending about two minutes on each case.

A recent audit of Iowa Medicaid records revealed how pharmacy benefit managers are using complicated and sophisticated approaches for handling prescription drug claims that ultimately overcharge taxpayers, a finding that underscores controversy surrounding these crucial middlemen in the pharmaceutical supply chain, STAT explains. The audit found that one large pharmacy benefit manager appeared to have made more than $100 million by adjusting the amount of money paid to pharmacies without passing some of the savings back to managed care plans working on behalf of the state, according to Iowa officials. The review scrutinized records from 2019 through 2021.

Continue to STAT+ to read the full story…