CP v2

Tag: Alzheimerio liga

  • Nukritote po 40-ies? Mokslininkai įspėja: tai gali būti ankstyvas demencijos signalas

    Nukritote po 40-ies? Mokslininkai įspėja: tai gali būti ankstyvas demencijos signalas

    Vienas nugriuvimas po 40 metų amžiaus gali būti siejamas su didesne demencijos rizika ateityje, rodo didelės apimties mokslinė apžvalga. Tyrėjai pabrėžia, kad pats kritimas nebūtinai sukelia demenciją, tačiau gali būti ankstyvas įspėjimas, kad organizme vyksta nepageidaujami pokyčiai.

    Analizėje apibendrinti 7 tyrimų duomenys, iš viso apėmę daugiau nei 2,9 milijono 40 metų ir vyresnių žmonių, kurie tyrimų pradžioje demencijos neturėjo. Palyginus grupes nustatyta, kad po vieno kritimo demencijos rizika buvo apie 20 proc. didesnė, o patyrusiems kelis kritimus ji didėjo iki maždaug 74 proc.

    Ką rodo skaičiai ir ką jie reiškia

    Keturiuose tyrimuose, kuriuose vertintas vėlesnis demencijos dažnis, maždaug 11,6 proc. žmonių, turėjusių kritimų istoriją, vėliau sulaukė demencijos diagnozės. Tarp neturėjusių kritimų istorijos demencija išsivystė rečiau, apie 7,7 proc. atvejų.

    Mokslininkai atkreipia dėmesį, kad tai yra ryšys, o ne įrodymas apie priežastį. Kitaip tariant, kritimai gali būti ir pasekmė ankstyvų neurologinių pokyčių, kurie dar nepasireiškė aiškiais atminties ar mąstymo sutrikimais.

    Trys galimi paaiškinimai

    Pirmasis mechanizmas susijęs su traumomis, ypač galvos. Žinoma, kad galvos smegenų sukrėtimai ir kitos galvos traumos gali didinti vėlesnių pažintinių sutrikimų riziką, todėl kritimas su rimtesniu sužeidimu gali tapti papildomu rizikos veiksniu.

    Antrasis paaiškinimas vadinamas bendra priežastimi: neurodegeneraciniai procesai gali prasidėti gerokai anksčiau nei oficiali demencijos diagnozė, o pusiausvyros, reakcijos ir dėmesio pokyčiai didina griuvimų tikimybę. Tokiu atveju kritimai būtų ne priežastis, o ankstyvas simptomas.

    Trečias scenarijus susijęs su užburtu ratu. Po kritimo dalis žmonių ima bijoti judėti, mažina fizinį aktyvumą ir socialinius kontaktus, o būtent jie laikomi svarbiais veiksniais, padedančiais lėtinti pažintinių funkcijų silpnėjimą.

    Kada verta sunerimti ir ką daryti

    Tyrėjai ragina gydytojus atidžiau stebėti vidutinio amžiaus ir vyresnius pacientus, kurie krenta pakartotinai, ypač jei kritimai ima kartotis be akivaizdžios priežasties. Tokiais atvejais gali būti tikslinga įvertinti ne tik traumų riziką, bet ir bendrą neurologinę bei pažintinę būklę.

    „Gydytojai turėtų išlikti ypač budrūs dėl pažintinių funkcijų silpnėjimo žmonėms, kurie vidutiniame ar vyresniame amžiuje patiria pasikartojančius kritimus“, – teigiama tyrėjų išvadose.

    Praktikoje tai gali reikšti kelis paprastus žingsnius: kritimų aplinkybių aptarimą, regos ir klausos patikrą, vaistų peržiūrą, pusiausvyros ir eisenos įvertinimą, o prireikus ir pažintinių funkcijų testus. Specialistai taip pat pabrėžia, kad kritimų prevencija, jėgos ir pusiausvyros treniruotės bei saugesnė namų aplinka svarbios ne tik kaulų ar traumų prevencijai, bet ir bendrai sveikatai.

    Nors dar reikia daugiau tyrimų, kad būtų tiksliau atskirta, kas šiame ryšyje yra priežastis, o kas ankstyvas požymis, bendras signalas aiškus: pasikartojantys kritimai po 40-ies nėra smulkmena. Tai proga laiku įvertinti sveikatą ir, jei reikia, imtis priemonių, kurios gali padėti anksčiau pastebėti rizikas.

  • Mokslininkus sudominusi medžiaga braškėse: siejama su „zombių ląstelių“ mažinimu

    Mokslininkus sudominusi medžiaga braškėse: siejama su „zombių ląstelių“ mažinimu

    Braškės dažniausiai siejamos su vitaminu C ir skaidulomis, tačiau jose yra ir fisetino – augalinio flavonoido, kuris pastaraisiais metais sulaukia vis daugiau mokslininkų dėmesio. Šis junginys aptinkamas ir obuoliuose, svogūnuose bei kituose augaliniuose produktuose, bet braškės dažnai minimos kaip vienas reikšmingesnių mitybinių šaltinių.

    Tyrimuose fisetinas siejamas su antioksidaciniu ir priešuždegiminiu poveikiu, taip pat su galimu neuroprotekciniu vaidmeniu. Mokslinėje literatūroje jis aptariamas ir kaip potencialus senolitikas – medžiaga, kuri gali padėti mažinti senstančių ląstelių kiekį organizme.

    Kas yra senstančios ląstelės?

    Senstančios ląstelės, kartais viešojoje erdvėje vadinamos zombių ląstelėmis, yra ląstelės, kurios nebesidalija, tačiau išlieka aktyvios. Jos gali išskirti uždegiminius signalus ir kitas medžiagas, galinčias neigiamai veikti aplinkinius audinius.

    Su amžiumi tokių ląstelių daugėja, o imuninė sistema ne visada jas pašalina pakankamai efektyviai. Dėl to senstančios ląstelės siejamos su lėtiniu, žemo intensyvumo uždegimu ir didesne įvairių su amžiumi susijusių būklių rizika.

    Ką rodo tyrimai apie fisetiną?

    Dalis eksperimentinių tyrimų su gyvūnais rodo, kad fisetinas gali mažinti senstančių ląstelių žymenis, o kartu ir uždegimo bei oksidacinio streso rodiklius. Kai kuriuose darbuose aprašoma, kad periodiškas fisetino vartojimas laboratorinėmis sąlygomis buvo siejamas su geresne audinių pusiausvyra ir palankesniais senėjimo ženklais.

    Vis dėlto svarbu pabrėžti, kad didelė dalis įrodymų yra gauta ląstelių kultūrose arba su gyvūnais, o žmonėms atliktų didelių, aukštos kokybės klinikinių tyrimų dar trūksta. Tai reiškia, kad teiginių apie tiesioginį poveikį ilgaamžiškumui ar konkrečių ligų prevencijai žmogui kol kas negalima laikyti galutinai patvirtintais.

    Kaip į tai žiūrėti praktiškai?

    Ekspertai paprastai sutaria, kad didžiausia nauda sveikatai vis dar siejama su bendrais mitybos principais: įvairiu augaliniu racionu, pakankamu skaidulų kiekiu, mažesniu perdirbtų produktų vartojimu ir reguliariu fiziniu aktyvumu. Braškės šiame kontekste gali būti vertinga kasdienės mitybos dalis, nes be fisetino jos suteikia vitaminų, antioksidantų ir skaidulų.

    Jei svarstoma apie fisetino papildus, verta pasitarti su gydytoju ar vaistininku, ypač vartojant receptinius vaistus ar turint lėtinių ligų. Papildų poveikis ir saugumas gali skirtis nuo to, kas stebima vartojant natūralius maisto produktus, o dozės tyrimuose neretai būna didesnės nei įprastai gaunamos su mityba.

  • Study hints ADHD could raise dementia risk, with brain iron and blood markers offering early clues

    Adults diagnosed with attention deficit hyperactivity disorder may face a higher risk of developing dementia later in life, according to new research from Geneva University Hospitals and the University of Geneva. The study links ADHD to biological changes often seen in age-related neurodegenerative disease.

    Researchers reported that adults with ADHD showed altered iron levels in specific brain regions and higher concentrations of a blood marker tied to nerve cell damage. Both signals have been associated in previous research with conditions such as Alzheimer’s disease.

    Brain iron and nerve damage marker

    The team examined 32 adults aged 25 to 45 with ADHD and 29 similarly aged healthy participants. Using an MRI technique called quantitative susceptibility mapping, they estimated iron content across brain areas and compared it with blood measurements.

    Participants with ADHD had different iron distribution in several regions, and iron in the precentral cortex was associated with higher neurofilament light chain levels in blood. Neurofilament light chain is widely used in neurology research as an indicator of ongoing neuronal injury.

    Why iron may matter

    Iron is essential for healthy brain function, but excess accumulation has been linked to oxidative stress and damage to neurons. In Alzheimer’s disease and other dementias, abnormal iron patterns have repeatedly been observed alongside other signs of degeneration.

    The authors argue that the combination of increased regional brain iron and elevated neurofilament light chain could point to an early neurobiological pathway that helps explain epidemiological links between ADHD and dementia. They emphasize, however, that the findings do not mean dementia is inevitable for people with ADHD.

    What this could change next

    With dementia affecting an estimated 55 million people worldwide and nearly 10 million new cases each year, identifying modifiable risks remains a major public health goal. Alzheimer’s disease accounts for roughly 60 to 70% of diagnoses, according to the World Health Organization.

    The researchers say larger, long-term studies are needed to confirm whether these markers predict later cognitive decline and whether interventions can alter risk. They also note the broader importance of recognizing and managing adult ADHD, both for day-to-day functioning and potential long-term brain health.

  • Cambridge study links menopause to grey matter decline, raising new questions about HRT and brain health

    Cambridge study links menopause to grey matter decline, raising new questions about HRT and brain health

    Menopause may be associated with measurable changes in brain structure, alongside higher rates of anxiety, depression and sleep disruption, according to new research led by the University of Cambridge using UK Biobank data.

    In a large sample of women, researchers reported lower grey matter volume in several brain regions after menopause, patterns that were broadly similar whether or not participants had used hormone replacement therapy, commonly known as HRT.

    What the researchers analyzed

    The team examined questionnaire, health and cognitive testing data from nearly 125 000 women in the UK Biobank, a long-running project that links health records with detailed participant assessments.

    They also reviewed brain MRI scans from around 11 000 women, allowing comparisons between those who were pre-menopause, post-menopause without HRT use, and post-menopause with HRT use.

    Mental health and sleep symptoms

    Across the dataset, women who had gone through menopause were more likely to report seeking medical help for anxiety, nervousness or depression, and they were more likely to report persistent sleep problems such as insomnia and fatigue.

    Women who used HRT showed higher levels of anxiety and depression than non-users, but the analysis suggested these differences often existed before menopause, indicating HRT may have been prescribed to people already experiencing symptoms.

    Brain regions tied to memory and emotion

    Imaging results showed reduced grey matter volume after menopause in areas involved in memory and emotional regulation, including the hippocampus, entorhinal cortex and anterior cingulate cortex.

    Because some of these regions are also affected early in Alzheimer’s disease, the findings add to ongoing research into why women are diagnosed with dementia more often than men, though the study does not prove menopause causes dementia.

    On cognitive testing, memory scores were broadly similar across groups, but reaction time tended to be slower after menopause, with evidence that HRT use was associated with a smaller decline in reaction speed.

    The authors emphasized that menopause can be a major health transition and argued for greater attention to mental health support, sleep and lifestyle measures such as exercise and diet, alongside individualized medical advice about HRT.

    The study was published in Psychological Medicine, and the researchers noted that further work is needed to clarify how hormone changes, symptom severity, HRT timing and other health factors interact with brain ageing.

  • Microplastics and the brain: Researchers map possible links to Alzheimer’s and Parkinson’s

    Microplastics and the brain: Researchers map possible links to Alzheimer’s and Parkinson’s

    Microplastics, the tiny plastic fragments found in food, water and household dust, are under growing scrutiny as researchers examine how they may affect the brain. A new scientific review pulls together evidence suggesting these particles could contribute to processes seen in Alzheimer’s and Parkinson’s disease.

    Dementia affects more than 57 million people globally, and experts expect the burden of neurodegenerative disease to rise as populations age. That backdrop is sharpening interest in whether environmental exposures such as microplastics may worsen inflammation or accelerate neurological decline.

    Five mechanisms under scientific review

    The review, published in Molecular and Cellular Biochemistry by an international team including the University of Technology Sydney and Auburn University, outlines several biological routes of potential harm. It focuses on immune activation, oxidative stress, disruption of the blood-brain barrier, mitochondrial dysfunction and direct neuronal injury.

    Researchers argue that if microplastics weaken the blood-brain barrier, the brain may become more vulnerable to inflammatory molecules and immune responses that can damage delicate tissue. In parallel, they describe how oxidative stress could rise if reactive oxygen species increase while antioxidant defenses are depleted.

    Energy disruption and protein buildup concerns

    Another concern highlighted in the paper is mitochondrial interference, which could reduce cellular energy production and strain neurons that rely heavily on steady ATP supply. Over time, energy shortfalls may impair brain function and make nerve cells more susceptible to damage.

    The authors also discuss disease-specific hypotheses, including whether microplastics might promote protein changes associated with Alzheimer’s, such as beta-amyloid and tau accumulation. For Parkinson’s, they note a possible role in α-synuclein aggregation and stress on dopamine-producing neurons.

    What the evidence can and cannot show

    While the review raises plausible pathways, the researchers stress that confirming a direct causal link in humans will require further studies, including exposure measurement and long-term clinical follow-up. Much of the current understanding comes from laboratory and animal research, along with emerging evidence that microplastics can accumulate in organs.

    Even with uncertainties, scientists say practical exposure reduction may be reasonable while research catches up, particularly in everyday food and household contexts. The authors point to reducing reliance on plastic food containers and packaging, limiting plastic-related dust and fibers, and supporting policies that curb plastic pollution at its source.

    Ongoing work at the involved institutions is expected to further test how ingested or inhaled microplastics interact with cells and barriers in the body. Public health experts say clearer answers will depend on standardizing how microplastics are measured and comparing real-world doses across populations.

  • Explainable AI tool CANYA decodes protein aggregation patterns, offering new clues for amyloid diseases and drug manufacturing

    An AI tool has made a step forward in translating the language proteins use to dictate whether they form sticky clumps similar to those linked to Alzheimer’s Disease and around fifty other types of human disease. In a departure from typical “black-box” AI models, the new tool, CANYA, was designed to be able to explain its decisions, revealing the specific chemical patterns that drive or prevent harmful protein folding.

    The discovery, published today in the journal Science Advances, was possible thanks to the largest-ever dataset on protein aggregation created to date. The study gives new insights about the molecular mechanisms underpinning sticky proteins, which are linked to diseases affecting half a billion people worldwide.

    Protein clumping, or amyloid aggregation, is a health hazard that disrupts normal cell function. When certain patches in proteins stick to each other, proteins grow into dense fibrous masses that have pathological consequences.

    While the study has some implications for accelerating research efforts for neurodegenerative diseases, it’s more immediate impact will be in biotechnology. Many drugs are proteins, and they are often hampered by unwanted clumping.

    “Protein aggregation is a major headache for pharmaceutical companies,” says Dr. Benedetta Bolognesi, co-corresponding author of the study and Group Leader at the Institute for Bioengineering of Catalonia (IBEC).

    “If a therapeutic protein starts aggregating, manufacturing batches can fail, costing time and money. CANYA can help guide efforts to engineer antibodies and enzymes that are less likely to stick together and reduce expensive setbacks in the process,” she adds.

    Protein clumps are formed using a poorly understood language. Proteins are made of twenty different types of amino acids. Instead of the usual A, C, G, T letters that make up the language of DNA, a protein’s language has twenty different letters, different combinations of which form “words” or “motifs.”

    Researchers have long sought to decipher which combinations of motifs cause clumping and which others enable proteins to fold without error. Artificial intelligence tools that treat amino acids like the alphabet of a mysterious language could help identify the precise words or motifs responsible, but the quality and volume of data about protein aggregation needed to feed models have been historically scant or restricted to very small protein fragments.

    The study addressed this challenge by carrying out large-scale experiments. The authors of the study created over 100,000 completely random protein fragments, each 20 amino acids long, from scratch. The ability for each synthetic fragment to clump was tested in living yeast cells. If a particular fragment triggered clump formation, the yeast cells would grow in a certain way that could be measured by the researchers to determine cause and effect.

    Around one in every five protein fragments (21,936/100,000) caused clumping, while the rest did not. While previous studies might have tracked a handful sequences, the new dataset captures a much bigger catalogue of the different protein variants which can cause amyloid aggregation.

    “We created truly random protein fragments including many versions not found in nature. Evolution has explored only a fraction of all possible protein sequences, while our approach helps us peer into a much bigger galaxy of possibilities, providing lots of data points to help understand more general laws of aggregation behaviour,” explains Dr. Mike Thompson, first author of the study and postdoctoral researcher at the Centre for Genomic Regulation (CRG).

    The vast amount of data generated from the experiments was used to train CANYA. The researchers decided to create it using the principles of “explainable AI,” making its decision-making processes transparent and understandable to humans. This meant sacrificing a little bit of its predictive power, which is usually higher in “black-box” AIs. Despite this, CANYA proved to be around 15% more accurate than existing models.

    Specifically, CANYA is a convolution-attention model, a hybrid tool borrowing from two distinct corners of AI. Convolution models, like those used in image recognition, scan photos for features like an ear or a nose to identify a face, except in this case CANYA skims through the protein chain to find meaningful features like motifs or “words.”

    Attention AI models are used by language translation tools to identify key phrases in a sentence before deciding on the best translation. The researchers incorporated this technique to help CANYA figure out which motifs matter most in the grand scheme of the entire protein.

    Together, these two approaches help CANYA see local motifs up close while also spotting their bigger-picture importance. The researchers could use this information to not just predict which motifs in the protein chain encourage clumping, block it, or something in between, but also understand why.

    For example, CANYA showed that small pockets of water-repelling amino acids are more likely to spark clumping, while some motifs have a bigger impact on clumping if they’re near the start of a protein sequence rather than at the end. The observations align with previous findings researchers have seen under the microscope in known amyloid fibrils.

    But CANYA also found new rules driving protein aggregation. For instance, certain building blocks of proteins, so-called charged amino acids, are normally thought to prevent clumping. But it turns out that in the context of other specific building blocks, they can actually promote clumping.

    In its current form, CANYA primarily explains protein aggregation in yes or no terms, i.e. it works as a so-called “classifier.” The researchers next want to refine the system so it can predict and compare aggregation speeds rather than just aggregation likelihood. This could help predict which protein variants form clumps quickly and which do so more slowly, a vital factor in neurodegenerative diseases where the timing of amyloid formation matters just as much as the fact that it happens at all.

    “There are 1024 quintillion ways of creating a protein fragment that is 20-amino acids long. So far, we’ve trained an AI with just 100,000 fragments. We want to improve it by making more and bigger fragments. This is just the first step but our work shows it is possible to decipher the language of protein aggregation. This is incredibly important for our understanding of human disease but also to guide synthetic biology efforts” concludes Dr. Bolognesi.

    “This project is a great example of how combining large-scale data generation with AI can accelerate research. It’s also a very cost-effective method to generate data,” says ICREA Research Professor Ben Lehner, co-corresponding author and Group Leader at the Centre for Genomic Regulation (CRG) and the Wellcome Sanger Institute.

    “Using DNA synthesis and sequencing we can perform hundreds of thousands of experiments in a single tube, generating the data we need to train AI models. This is an approach we are applying to many difficult problems in biology. The goal is to make biology predictable and programmable,” he adds.

    The study is a joint collaborative effort by ICREA Research Professor Ben Lehner’s lab at the Centre for Genomic Regulation (CRG) and Benedetta Bolognesi’s lab at the Institute for Bioengineering of Catalonia (IBEC). Researchers from Cold Spring Harbor Laboratory (CSHL) and Wellcome Sanger Institute also collaborated in the study. It was funded by “La Caixa” Research Foundation, the European Research Council and the Spanish Ministry of Science and Innovation.

  • New Alzheimer’s study points to subtle brain blood flow changes as an early warning sign

    New Alzheimer’s study points to subtle brain blood flow changes as an early warning sign

    Small shifts in how blood moves through the brain and how brain cells receive oxygen may be closely connected to the risk of Alzheimer’s disease. That is the conclusion of new research from the Mark and Mary Stevens Neuroimaging and Informatics Institute (Stevens INI) at the Keck School of Medicine of USC.

    The study, published in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association, examined older adults both with and without cognitive impairment. Researchers found that simple, noninvasive measures of brain blood flow and oxygen levels were linked to well known signs of Alzheimer’s, including amyloid plaque buildup and shrinkage of the hippocampus, the part of the brain that plays a central role in memory. The results suggest that the health of the brain’s blood vessels may influence the disease process early on and could help flag people at risk before noticeable symptoms develop.

    “Amyloid and tau are often considered the primary players in Alzheimer’s disease, but blood flow and oxygen delivery are also critical,” said Amaryllis A. Tsiknia, lead author of the study and USC PhD candidate. “Our results show that when the brain’s vascular system functions more like it does in healthy aging, we also see brain features that are linked to better cognitive health.”

    Noninvasive Tools to Measure Brain Circulation

    To study these changes, the team relied on two painless techniques that can be used while a person rests quietly. Transcranial Doppler ultrasound tracks how quickly blood travels through the brain’s major arteries. Near infrared spectroscopy evaluates how effectively oxygen reaches brain tissue near the surface of the cortex.

    Researchers then applied advanced mathematical modeling to combine these readings into overall indicators of cerebrovascular function. These indicators reflect how well the brain adjusts blood flow and oxygen delivery in response to natural fluctuations in blood pressure and carbon dioxide.

    Vascular Health Linked to Amyloid and Memory Centers

    Participants whose vascular indicators more closely resembled those of cognitively healthy adults tended to have lower amyloid levels and a larger hippocampus. Both features are associated with reduced Alzheimer’s risk.

    “These vascular measures are capturing something meaningful about brain health,” said Meredith N. Braskie, PhD, senior author of the study and assistant professor of neurology at the Keck School of Medicine. “They appear to align with what we see on MRI and PET scans that are commonly used to study Alzheimer’s disease, providing important information about how vascular health and standard brain measures of Alzheimer’s disease risk may be related.”

    The researchers also observed that people diagnosed with mild cognitive impairment or dementia showed weaker vascular function compared to cognitively normal participants. This finding supports the view that declining blood vessel health in the brain is part of the broader Alzheimer’s disease continuum.

    “These findings add to growing evidence that Alzheimer’s involves meaningful vascular contributions in addition to classic neurodegenerative changes,” said Arthur W. Toga, PhD, director of the Stevens INI. “Understanding how blood flow and oxygen regulation interact with amyloid and brain structure opens new doors for early detection and potentially prevention.”

    Potential for Earlier and Broader Screening

    Compared with MRI and PET imaging, these methods are less costly and easier to perform. They do not involve injections, radiation exposure, or demanding tasks for patients. That simplicity could make them useful for large scale screening or for individuals who are unable to undergo more intensive brain imaging.

    The authors caution that the findings represent a single snapshot in time and do not establish cause and effect. Ongoing long term studies are tracking participants to see whether shifts in these vascular measures can predict future cognitive decline or response to treatment.

    “If we can track these signals over time, we may be able to identify people at higher risk earlier and test whether improving vascular health can slow or reduce Alzheimer’s-related brain changes,” Tsiknia said.

    About the Study

    In addition to Tsiknia and Braskie, the study’s other authors are Peter S. Conti, Rebecca J. Lepping, Brendan J. Kelley, Rong Zhang, Sandra A. Billinger, Helena C. Chui and Vasilis Z. Marmarelis.

    This work was supported by the Office of The Director, National Institutes of Health, under Award Number S10OD032285, and by the National Institute on Aging [R01AG058162].

  • AI-built molecular atlas maps Alzheimer’s brain beyond amyloid plaques, pointing to overlooked metabolic shifts

    AI-built molecular atlas maps Alzheimer’s brain beyond amyloid plaques, pointing to overlooked metabolic shifts

    Researchers at Rice University have created a label-free molecular atlas of the Alzheimer’s brain in an animal model, using laser-based imaging paired with artificial intelligence. The work aims to clarify how the disease emerges and spreads beyond what standard pathology typically captures.

    The study used hyperspectral Raman imaging, an advanced form of Raman spectroscopy that reads chemical fingerprints in tissue without dyes or fluorescent tags. By scanning brain slices at high resolution, the team generated a detailed chemical map designed to reflect the brain’s native state.

    What the imaging revealed

    Analysis indicated that Alzheimer’s-linked chemical changes were not limited to amyloid plaques. Instead, the alterations appeared across multiple brain regions, with uneven patterns that could help explain why symptoms develop gradually and differ between individuals.

    To handle the large dataset, the researchers applied both unsupervised and supervised machine learning methods. Unsupervised tools grouped tissue by molecular similarity, while supervised models helped distinguish Alzheimer’s-affected samples from controls across different regions.

    Metabolic signals in key regions

    Beyond protein-related pathology, the maps pointed to broader metabolic differences, including shifts in cholesterol and glycogen signals. The strongest contrasts were reported in brain regions central to memory and cognition, including the hippocampus and cortex.

    The authors argue that these molecular patterns support a wider view of Alzheimer’s as a disorder involving disrupted brain structure and energy balance, not only plaque formation. They say a whole-brain, label-free approach could help surface changes that targeted assays might miss.

    While the findings are based on an animal model and would need validation in human tissue, the researchers suggest the approach could eventually inform earlier detection strategies and more region-specific treatment research. The study was published in ACS Applied Materials and Interfaces with support from U.S. federal research funders.

  • Loss of Smell May Signal Early Alzheimer’s: New Study Points to an Immune Trigger

    Loss of Smell May Signal Early Alzheimer’s: New Study Points to an Immune Trigger

    A subtle decline in the sense of smell could be among the earliest detectable changes linked to Alzheimer’s disease, potentially emerging well before clear memory problems. New research from Germany suggests the shift may be driven by the brain’s immune cells damaging key odor-processing connections.

    The study, led by scientists at the German Center for Neurodegenerative Diseases (DZNE) and Ludwig Maximilian University of Munich, focuses on microglia, immune cells that help maintain brain health. Researchers report that in early Alzheimer’s, microglia may begin dismantling nerve fibers needed for normal smell perception.

    How the brain’s smell circuit changes

    The team examined communication between the olfactory bulb, which processes odor signals, and the locus coeruleus, a brainstem region involved in sensory regulation and other core functions. Long nerve fibers from the locus coeruleus help tune activity in the olfactory bulb, supporting normal smell processing.

    According to the researchers, early Alzheimer’s-related alterations make these fibers appear abnormal to microglia. In response, microglia break down the connections, which could help explain why smell deficits can appear early in the disease course.

    An eat-me signal on neurons

    The study points to changes in the nerve fiber membrane as a likely trigger. A molecule called phosphatidylserine, typically kept on the inner side of the cell membrane, was observed on the outside, where it can act as an immune cue.

    Microglia are known to respond to this kind of signal during normal synaptic pruning, a process that removes unused or impaired connections. The researchers suggest that in early Alzheimer’s, abnormal neuron activity may prompt this membrane shift, leading microglia to remove fibers that are still needed.

    Evidence from mice, tissue, and PET scans

    To support the mechanism, the scientists combined results from Alzheimer’s-like mouse models with analyses of human brain tissue and PET imaging data from people diagnosed with Alzheimer’s or mild cognitive impairment. Together, these lines of evidence point to immune-driven damage occurring at an early stage.

    The findings also connect to a growing push for earlier diagnosis, as newer Alzheimer’s treatments are generally aimed at earlier phases of the disease. Researchers say a better understanding of smell-related changes could help identify people who should receive further testing before cognitive symptoms become pronounced.

    Smell loss can have many causes, including aging, infections, allergies, and other neurological conditions, so it is not a stand-alone diagnostic sign. Still, the study strengthens the case that changes in olfaction may offer a practical early clue worth taking seriously in Alzheimer’s research and clinical follow-up.

  • Johns Hopkins study spotlights hydrogen sulfide signaling as a potential new target in Alzheimer’s research

    Johns Hopkins study spotlights hydrogen sulfide signaling as a potential new target in Alzheimer’s research

    Researchers at Johns Hopkins Medicine report that a newly funded study by the National Institutes of Health is helping advance a potential new approach to Alzheimer’s disease treatment. The focus is a protein in the brain that produces a small but important gas.

    The protein, called Cystathionine γ-lyase, or CSE — best known for generating hydrogen sulfide, the gas that smells like rotten eggs — appears to play a key role in how memory forms. The findings come from experiments in genetically engineered mice, according to study leader Bindu Paul, M.S., Ph.D., associate professor of pharmacology, psychiatry and neuroscience at the Johns Hopkins University School of Medicine.

    The research, published in Proceedings of the National Academy of Sciences, aims to better understand how this protein works and whether boosting its activity could help protect brain cells and slow neurodegenerative diseases such as Alzheimer’s.

    Hydrogen Sulfide May Protect Brain Cells

    Earlier studies suggested that hydrogen sulfide can help protect neurons in mice. However, the gas is toxic in large amounts, which makes it unsafe to deliver directly to the brain. Scientists are instead trying to understand how to safely maintain the extremely small levels naturally present in neurons.

    The new findings show that mice engineered to lack the CSE enzyme develop problems with memory and learning. These mice also show increased oxidative stress, DNA damage and weakened blood-brain barrier integrity — all features commonly associated with Alzheimer’s disease, says Paul, the study’s corresponding author.

    Building on Years of Research

    The current work builds on earlier research led by Solomon Snyder, M.D., D.Sc., D.Phil., professor emeritus of neuroscience, pharmacology, and psychiatry. In 2014, his team reported that CSE supported brain health in mice with Huntington’s disease. The researchers used mice lacking the CSE protein, first developed in 2008 when the protein was linked to blood vessel function and blood pressure regulation.

    In 2021, the group found that CSE was not functioning properly in mice with Alzheimer’s disease, and that very small injections of hydrogen sulfide helped protect brain function.

    Those earlier studies focused on mice with additional genetic mutations tied to neurodegenerative diseases. The latest research isolates the role of CSE itself.

    “This most recent work indicates that CSE alone is a major player in cognitive function and could provide a new avenue for treatment pathways in Alzheimer’s disease,” says co-corresponding author Snyder, who retired from the Johns Hopkins Medicine faculty in 2023.

    Memory Loss Linked to CSE Deficiency

    To better understand how CSE affects memory, scientists compared mice lacking the protein with normal mice using the same strain developed in 2008. They tested spatial memory (ability to remember directions and follow cues) using a setup called the Barnes maze.

    In this test, mice learn to escape a bright light by finding a hidden shelter. At two months old, both normal mice and those lacking CSE performed similarly, locating the shelter within three minutes. By six months, however, the CSE-deficient mice struggled to find the escape route, while normal mice continued to succeed.

    “The decline in spatial memory indicates a progressive onset of neurodegenerative disease that we can attribute to CSE loss,” says first author Suwarna Chakraborty, a researcher in Paul’s lab.

    Brain Changes Mirror Alzheimer’s Disease

    The researchers also examined how the absence of CSE affects the brain at a cellular level. The hippocampus, a region critical for learning and memory, relies on the formation of new neurons. Disruptions in this process are a known feature of neurodegenerative diseases.

    Using biochemical and analytical methods, the team found that proteins involved in neurogenesis were reduced or missing in mice without CSE.

    With high powered electron microscopes, the scientists observed structural damage in the brains of these mice. They found large breaks in blood vessels, indicating harm to the blood-brain barrier, another hallmark of Alzheimer’s disease. In addition, newly formed neurons had difficulty reaching the hippocampus, where they normally contribute to memory formation.

    “The mice lacking CSE were compromised at multiple levels, which correlated with symptoms that we see in Alzheimer’s disease,” says co-first author Sunil Jamuna Tripathi, a researcher in Paul’s lab.

    Toward New Alzheimer’s Treatments

    Alzheimer’s disease affects more than 6 million people in the United States, according to the U.S. Centers for Disease Control and Prevention, and the number continues to grow. Currently, no treatments have been consistently shown to stop or slow the disease.

    The researchers say that targeting CSE and its production of hydrogen sulfide could offer a new path for developing therapies aimed at protecting brain function and slowing disease progression.

    Funding and Research Contributors

    Funding support for this research was provided by the National Institutes of Health (1R01AG071512, P50 DA044123,1R21AG073684, O1AGs066707, U01 AG073323, AG077396, NS101967, NS133688, P01CA236778), the Department of Defense (HT94252310443), the American Heart Association, AHA-Allen Initiative in Brain Health and Cognitive Impairment, the Solve ME/CFS Initiative, the Catalyst Award from Johns Hopkins University, the Valour Foundation, the Wick Foundation, Department of Veterans Affairs Merit Award (I01BX005976), the Louis Stokes Cleveland Department of Medical Affairs Veterans Center, the Mary Alice Smith Funds for Neuropsychiatry Research, the Lincoln Neurotherapeutics Research Fund, the Gordon and Evie Safran Neuropsychiatry Fund; and the Leonard Krieger Fund of the Cleveland Foundation.

    In addition to Paul, Snyder, Chakraborty and Tripathi, contributors included Richa Tyagi and Benjamin Orsburn from Johns Hopkins; Edwin Vázquez-Rosa, Kalyani Chaubey, Hisashi Fujioka, Emiko Miller and Andrew Pieper of Case Western University; Thibaut Vignane and Milos Filipovic from Leibniz Institute for Analytical Sciences, Germany; Sudarshana Sharma from Hollings Cancer Center; Bobby Thomas from Darby Children’s Research Institute and the Medical University of South Carolina, and Zachary Weil and Randy Nelson from West Virginia University School of Medicine.