News

Beyond Alzheimer’s: Quantum AI hunts new uses for XPro

INmune Bio is pairing a quantum machine with AI to find diseases beyond Alzheimer’s that its drug candidate might help. Drug developers usually pick a disease and go looking for a molecule to treat it. INmune Bio has flipped that around. It already holds a molecule, an investigational Alzheimer’s treatment called XPro (XPro1595), and it […] The post Beyond Alzheimer’s: Quantum AI hunts new uses for XPro appeared first on Longevity.Technology.

NRG Therapeutics launches brain-tracking study for new neurodegenerative drug

NRG Therapeutics has started a PET imaging biodistribution trial (NRG5051-102) of its lead clinical asset NRG5051. The company says it has successfully radiolabelled NRG5051 and initiated PET scans in healthy volunteer participants in London to demonstrate central nervous system penetration and to inform dose selection for future patient trials. The study is designed to determine […] The post NRG Therapeutics launches brain-tracking study for new neurodegenerative drug appeared first on Longevity.Technology.

Muna Therapeutics’ Alzheimer’s drug MNA-001 passes early safety trial

Muna Therapeutics announced positive Phase 1 results for MNA-001, an oral small-molecule modulator of TREM2. The randomized, double-blind, placebo-controlled study assessed single- and multiple-ascending doses in younger volunteers, with an additional elderly cohort. There were no serious adverse events or discontinuations for adverse events, and most adverse events were mild. The company reports MNA-001 achieved […] The post Muna Therapeutics’ Alzheimer’s drug MNA-001 passes early safety trial appeared first on Longevity.Technology.

FDA clears NeuroXT’s AI software to assess Alzheimer’s progression risk

NeuroXT Inc. has received 510(k) clearance from the U.S. Food and Drug Administration for NEXT-Cue, an AI-based software-as-a-medical-device classified as Class II. NEXT-Cue integrates brain MRI images, demographic information, and cognitive assessment data to provide supplementary information to help clinicians assess patients with mild cognitive impairment for progression to Alzheimer’s dementia within five years. The […] The post FDA clears NeuroXT’s AI software to assess Alzheimer’s progression risk appeared first on Longevity.Technology.

Cognition Therapeutics gets FDA alignment for Phase 3 Zervimesine trial

Cognition Therapeutics announced alignment with the U.S. Food and Drug Administration on key elements of a planned pivotal Phase 3 registrational study of Zervimesine (CT1812) in dementia with Lewy bodies. The planned study is expected to enroll participants with mild-to-moderate DLB who will be randomized to receive 100 mg once-daily oral Zervimesine or placebo for […] The post Cognition Therapeutics gets FDA alignment for Phase 3 Zervimesine trial appeared first on Longevity.Technology.

PLA2G2F is Protective of Memory Function in the Aging Brain

Researchers here identify the gene PLA2G2F as a regulator of compensatory responses to some of the damage and dysfunction of aging. The researchers were primarily investigating a population of neurons found in the hippocampus, involved in memory function, but find that the gene is relevant in supporting cells of the brain also, such as microglia. Expression of PLA2G2F increases with age, and artificially increasing expression over natural levels produces greater protection. PLA2G2F appears to be involved in maintenance of normal lipid metabolism. Evidence suggests that dysfunctions in lipid metabolism occur in the aging brain, and cause harm via provoking greater inflammatory behavior in a number of supporting cell populations. Cognitive reserve theory posits that compensatory mechanisms during aging stave off cognitive decline and lower risk […]

The APOEε4 Variant Interferes in Myelination in the Aging Brain

Of the common variants of the APOE gene, APOEε4 presents the greatest risk of Alzheimer's disease. APOE is involved in lipid metabolism, and APOEε4 is associated with lipid-related contributions to inflammation in microglia, suggesting a primarily inflammatory mechanism for the increased risk of neurodegeneration. Here, researchers find that APOEε4 also interferes in the ability of oligodendrocyte cells to maintain the myelin structures that sheath the axons that connect neurons into neural networks, again via lipid-related mechanisms. This myelin sheathing is required for effective communication between neurons. Myelin maintenance does falter to some degree in normal aging, and the consequent loss of myelin is thought to contribute to dysfunction in the aging brain. It is reasonable to hypothesize that greater myelin loss driven by APOEε4 is […]

An AI-driven model for risk stratification and prototype intervention mapping in motoric cognitive risk syndrome and subjective cognitive decline

As Alzheimer's disease and other dementias continue their global rise, there is a compelling need for early identification of pre-clinical cognitive decline. Motoric Cognitive Risk Syndrome and Subjective Cognitive Decline represent crucial transition phases to facilitate targeted intervention, and existing unimodal approaches are neither sensitive nor sufficiently multimodal for appropriate risk classification and individualized intervention mapping (prototype). This study introduces a hybrid multimodal CNN fusion framework based on an improved version of light spectrum optimizer as metaheuristic optimizer to address this challenge. The framework fuses multiple modality-specific information through parallel three-dimensional convolutional neural network branches (MRI and PET) and encoders of motor, cognitive, and biomarker information followed by a combination of intermediate and late f

Increased LINE-1 expression is associated with neuronal gene network downregulation in the aged mouse prefrontal cortex

BackgroundAging is associated with epigenetic alterations, neuroinflammation, and progressive decline of neuronal function. Derepression of the retrotransposon LINE-1 (L1) has been implicated in aging and age-related diseases. However, the regional expression of L1 and its relationships with DNA methylation, genomic L1 copy number, and aging-related transcriptional changes in the normal aging brain remain incompletely understood.MethodsWe examined L1 expression in the prefrontal cortex (PFC), hippocampus, and nucleus accumbens of young (17-week-old, n = 10) and aged (101-week-old, n = 7) male C57BL/6J mice. L1 expression, DNA methylation, and genomic copy number were quantified by RT-qPCR, pyrosequencing, and genomic qPCR, respectively. Transcriptomic alterations in the PFC were analyzed by RNA-seq, followed by weighted gene co-expression network analysis (WGCNA).ResultsL1 expression was

Systems biology prioritizes drug candidates for an interferonresponse-high monocyte state in idiopathic normal pressure hydrocephalus

BackgroundIdiopathic normal pressure hydrocephalus (iNPH) is an age-associated neurological disorder characterized by gait disturbance, cognitive impairment, and urinary dysfunction. Although cerebrospinal fluid dynamics are central to its pathophysiology, the contribution of peripheral immune alterations remains poorly understood. We characterized an interferon-response-high monocyte state observed in iNPH and evaluated computational compound prioritization.MethodsWe used a fixed set of marker criteria to characterize the IFN-response-high monocyte state. We then compared monocyte clusters 5 and 0 and used 150 upregulated and 150 downregulated genes to screen compounds in LINCS. We tested whether candidate rankings changed with different state definitions, comparison groups, gene-list sizes, clustering settings, and inclusion of all patients. We also repeated the queries after excluding

Editorial: Decoding the gut-brain axis: implications for neurodegenerative disease therapies

Reprogramming the gut–brain axis in neurodegeneration: comparative microbiome, metabolite, immunometabolic, polyphenol, probiotic, and epigenetic mechanisms in Alzheimer’s and Parkinson’s diseases

The gut–brain axis has emerged as a central mechanistic framework linking dietary bioactives, microbial ecology, and neurodegenerative disease progression. Similar microbiome-related mechanisms have also been implicated in colorectal cancer, suggesting potential shared links between microbial dysbiosis, inflammation, and disease progression. This study synthesizes preclinical evidence examining how polyphenols, polyphenol-derived compounds, and advanced delivery systems, including nanoparticles and synbiotics, modulate Alzheimer’s disease (AD) and Parkinson’s disease (PD) through microbiome-dependent mechanisms. Evidence from transgenic mice, toxin-induced rodent models, and Drosophila systems was compared across microbiome alterations, microbial metabolites, signaling pathways, epigenetic regulation, and functional outcomes. Across AD and PD models, dietary bioactives consistently promo

Microbial metabolites as modulators of gut–brain communication in neurodegeneration: from intestinal sensing to disease initiation and progression

How heterogeneous gut metabolite alterations relate to Parkinson’s disease (PD) and Alzheimer’s disease (AD) remains unresolved. We propose a framework in which intestinal sensing of indole derivatives, short-chain fatty acids and bile acids links microbial function to barrier regulation and gut–brain communication. Integration denotes tissue-level convergence of aryl hydrocarbon receptor (AhR), pregnane X receptor (PXR) and metabolite-responsive G-protein-coupled receptor responses across epithelial and neighbouring immune cells, rather than an established same-cell receptor complex. Tryptophan metabolism provides an analytical focus connecting microbial indole production with host kynurenine and serotonin pathways; metabolite concentrations alone do not establish pathway flux or receptor activity. We hypothesise that suppressed indole-associated epithelial signalling, barrier hyperperm

Topical Urolithin A to Improve Aged Skin Function

Mitochondria are the power plants of the cell, creating the chemical energy store molecule adenosine triphosphate used to power cellular processes. Mitochondrial function declines with age, and the research community is engaged in a variety of approaches that might at least modestly reduce this loss. The supplement urolithin A is known to improve mitochondrial function, though, and as is the case for other approaches, how exactly urolithin A accomplishes this outcome is not fully understood. Most of the ways to modestly improve mitochondrial function, ranging from exercise and calorie restriction through to NAD+ upregulation via vitamin B3 derivatives and MitoQ, may primarily function through improvements to autophagy targeted at mitochondria, improving overall mitochondrial function via improved clearance of damaged and dysfunctional mitochondria. This is by […]

Millions take fish oil for brain health. A two-year study found no benefit

A surprising two-year clinical trial found that fish oil supplements successfully delivered omega-3s to the brain but failed to improve memory or protect against Alzheimer's-related brain shrinkage. Researchers suspect that getting these nutrients through a healthy diet may offer benefits that supplements alone cannot provide.

Lewy body drug candidate gets patent cover to 2045

Cognition Therapeutics wins a US patent on a new crystal form of zervimesine and has an FDA meeting on its Lewy body trial lined up. Cognition Therapeutics announced that its lead drug candidate, zervimesine (CT1812), now has patent protection running to 2045. The US Patent and Trademark Office granted a patent on a novel crystalline […] The post Lewy body drug candidate gets patent cover to 2045 appeared first on Longevity.Technology.

NeuroXT earns FDA clearance for AI brain scan analyzer for Alzheimer’s

NeuroXT Inc announced that NEXT-Cue, its AI-based Software as a Medical Device supporting prognostic assessment in patients with mild cognitive impairment, has received 510(k) clearance from the U.S. Food and Drug Administration as a Class II medical device. NEXT-Cue integrates brain MRI images, demographic data and cognitive assessment results to provide supplementary information intended to […] The post NeuroXT earns FDA clearance for AI brain scan analyzer for Alzheimer’s appeared first on Longevity.Technology.

Reduced weighted permutation entropy in visual-temporal cortex and altered resting-state brain dynamics in Alzheimer’s disease

BackgroundAlzheimer’s disease (AD) is increasingly recognized as a disorder of distributed neural dynamics. Resting-state fMRI combined with signal-complexity measures may provide new insights into alterations in spontaneous brain activity. This study investigated whether weighted permutation entropy (WPE), an amplitude-sensitive measure of temporal complexity, could identify regional abnormalities in AD and characterize their temporal and network-level features.MethodsTwenty patients with AD and twenty-four healthy controls underwent resting-state fMRI. Regional WPE was calculated using the Brainnetome atlas. Group comparisons included age, sex, years of education, and mean framewise displacement as covariates. Brainnetome findings were evaluated at an exploratory uncorrected threshold of p < 0.001 and checked against Bonferroni correction across 246 regions. Selected regions were used

Cross-cohort generalization limitations in gut microbiome-based Alzheimer’s disease classifiers: evidence from four supervised cohorts with batch-correction analysis

Gut microbiome dysbiosis has been proposed as an Alzheimer’s disease (AD) biomarker, but the transportability of microbiome classifiers across independent cohorts remains uncertain. We reprocessed five public 16S rRNA cohorts (509 samples, China, Kazakhstan, South Korea) with a common DADA2/genus-level pipeline and evaluated logistic regression and LightGBM classifiers using nested within-cohort cross-validation, leave-one-cohort-out (LOCO) transfer, pairwise transfer, permutational multivariate analysis of variance (PERMANOVA), batch adjustment, and out-of-fold SHapley Additive exPlanations (SHAP) analyses. Within four labeled cohorts, using strict training-only genus selection as the primary classifier-performance pipeline (Section 2.5.1), within-cohort area under the receiver operating characteristic curve (AUC-ROC) ranged from 0.611 to 0.996. The near-perfect Li 2019 result was stabl

Cerebrospinal fluid neurofilament heavy protein levels associated with domain-specific cognitive decline in Alzheimer’s disease

BackgroundNeurofilament proteins are fluid biomarkers of neuroaxonal damage in various neurological diseases. However, it remains to be elucidated whether CSF neurofilament heavy (NfH) protein levels correlate with cognitive decline and progression in Alzheimer’s disease (AD).MethodsThis study included 165 cognitively unimpaired (CU) participants, 385 participants with mild cognitive impairment (MCI), and 128 participants with AD. To examine correlations between CSF NfH levels and baseline cognitive measures, Pearson’s correlation was used. Linear mixed-effects models were fitted to assess the relationship between elevated CSF NfH levels and longitudinal cognitive decline in the CU, MCI and AD groups. Kaplan–Meier survival analyses and Cox proportional hazards models were used to assess the clinical progression in the CU and MCI groups separately.ResultsIn the MCI group, higher CSF NfH l

Blood sensor hunts Parkinson’s signals in 40 minutes

KAUST and Oxford researchers used a transistor-based sensor to read three forms of alpha-synuclein, reaching 90.9% accuracy in a small study. Blood is a messy place to go looking for brain clues. More than 95% of the alpha-synuclein floating around in it comes from red blood cells, and the small share that might say something […] The post Blood sensor hunts Parkinson’s signals in 40 minutes appeared first on Longevity.Technology.

Hearing Aid Use Correlates with Reduced Mortality Risk

The manifestations of aging, such as age-related diseases and mortality, all arise from the same underlying root cause mechanisms of damage and dysfunction. If an individual exhibits evident consequences of aging in one part of the body, in the form of a specific age-related condition, it is likely that the burden of damage and dysfunction throughout the body is high enough to cause other specific age-related conditions to arise as well. It doesn't necessarily mean that the conditions are linked in any way other than being consequences of the same processes. That said, aging is complex, everything in the body and brain is connected to at least some degree, and dysfunction in one system often does add to the dysfunction of other systems in ways […]

Circulating inflammatory biomarkers as adjusted prognostic predictors of post-stroke cognitive impairment: a comparative meta-analysis of cytokines and lymphocyte-based ratio indices in prospective cohorts

IntroductionSystemic inflammation is implicated in post-stroke cognitive impairment (PSCI). Two families of blood markers have been studied as predictors: cytokines (interleukin-6, C-reactive protein) and lymphocyte-based ratio indices from the full blood count, including the neutrophil-to-lymphocyte ratio, the systemic immune-inflammation index (SII) and the globulin-to-lymphocyte ratio (GLR). Existing syntheses pool unadjusted marker differences within a single family, so their relative adjusted associations with PSCI are unknown.MethodsWe systematically reviewed strictly prospective cohorts reporting a covariate-adjusted association between a circulating inflammatory marker and PSCI. Estimates were harmonised to the odds ratio per one standard deviation (SD) increase, deriving SDs where needed from medians and interquartile ranges and rescaling category contrasts by category-spacing f

Small-fiber degeneration, sensory dysfunction, and nociception comorbidity in central neurodegenerative disease

Progressive neurodegenerative disease typically calls for clinical effort to improve cognitive and motor deficits. It is also focused on improving patients' quality of life. However, across these dementias and other diseases, the underlying causes and potential mechanisms remain unclear. Most experimental and clinical research focuses on the central nervous system, examining pathogenic proteins such as tau and amyloid beta, as well as the potential cascade following mitochondrial damage and neuroinflammation. Although peripheral involvement, including gut microbiome influences and other visceral organs, is well-documented, the peripheral nervous system remains an understudied component of these progressive diseases. As peripheral terminals of primary afferent neurons are exposed to inflammatory or toxic mediators, these neurons respond to these threats via neuron-specific phenotypic chan

Rapid eye movement sleep behavior disorder as a model of early neurodegeneration: challenges for research and clinical diagnosis

Rapid eye movement (REM) sleep behavior disorder (RBD) has evolved from a descriptive parasomnia to a clinically informative model for studying early neurodegenerative processes, particularly within the spectrum of α-synucleinopathies. Defined by the loss of REM sleep atonia and the emergence of dream enactment behaviors, RBD reflects dysfunction of brainstem circuits that normally suppress motor output during dreaming. Longitudinal evidence indicates that many individuals with isolated RBD eventually develop neurodegenerative disease, most commonly Parkinson’s disease, dementia with Lewy bodies, or, less frequently, multiple system atrophy, positioning RBD among the most specific clinical markers of prodromal synucleinopathy currently recognized. Mechanistic studies suggest that RBD arises from instability within distributed REM sleep regulatory networks involving dopaminergic, noradren

Correction: Transcranial direct current stimulation to improve cognitive function in patients with vascular cognitive impairment: a literature review

Donated human brains may soon be studied for two weeks

An up to $28.3 million ARPA-H award aims to stretch Bexorg’s human brain platform from 24 hours to two weeks. A day is a long time to study a donated human brain. Bexorg thinks it’s still too short. On 7 October, the Connecticut-based company announced that it has been awarded up to $28.3 million by […] The post Donated human brains may soon be studied for two weeks appeared first on Longevity.Technology.

Your aging brain may be trading memory for something more valuable

The aging brain may be undergoing a remarkable transformation rather than simply losing its abilities, shifting its focus from remembering details to understanding the bigger picture. Scientists suggest this change could be an evolutionary adaptation that helps older adults develop wisdom and share decades of knowledge with younger generations.

Evidence for Peroxisome Dysfunction to be Important in Alzheimer's Disease is Not Conclusive

Peroxisomes in cells are responsible for helping to maintain oxidative metabolism via making and removing hydrogen peroxide, but are also involved in numerous aspects of lipid metabolism, breaking down or converting various lipids necessary to cell function. They have other, less well mapped functions relating to defense against pathogens. There is some evidence for peroxisome loss to occur with age, for this to be a meaningful cause of further cellular dysfunction. As researchers note here, however, the evidence for forms of peroxisome dysfunction to contribute meaningfully to Alzheimer's disease is suggestive but far from conclusive. As is often the case, the fastest path to clarity would be an approach to restore a more youthful peroxisome function to cells in the brain and elsewhere, and see […]

Scientists find a way to fight Alzheimer’s brain damage without removing toxic tau

Scientists have found a promising way to protect the brain from Alzheimer’s-related damage by blocking immune cells that contribute to the destruction of neurons. In mice, the treatment preserved roughly 40% more tissue in memory centers and improved memory, even without removing harmful tau protein buildup.

Decline in mitochondrial health and lysosomal acidification in human neurons during normal aging

IntroductionIn humans, aging is associated with an increased risk of developing neurodegenerative diseases such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). In neurons, the effect of aging on intrinsic molecular processes, and how they tie to age-related neurodegeneration remains unclear. Animal studies have shown that mitochondrial function decline, autophagy impairment and defective elimination of damaged mitochondria by mitophagy are all central features of neuronal aging. However, very few studies have investigated such events in human neurons, due to a lack of models showing aging features. Therefore, there is a crucial need for a better understanding of the effect of aging on neuronal health.MethodsHere, we use direct neuronal reprogramming, which maintains signatures of cellular aging, to study the effect of aging on mitochondrial health and mitophagy in human neurons

Brain structure–function decoupling and neuromuscular coordination during gait and sit-to-stand in healthy aging

BackgroundAge-related decline in lower-limb motor function reflects complex interactions between central brain networks and peripheral neuromuscular coordination. This study examined how structural–functional brain organization relates to muscle coordination, intermuscular coupling, and biomechanical control during gait and sit-to-stand (STS) tasks.MethodsIn this exploratory multimodal study, thirteen healthy young adults and sixteen healthy older adults underwent resting-state fMRI, DTI, surface electromyography, motion capture, plantar pressure, and ground reaction force measurements. Muscle synergy similarity, intermuscular coherence (IMC), IMC network efficiency, center-of-pressure (COP), ground reaction force (GRF), and structure–function decoupling index (SDI) were quantified and analyzed.ResultsOlder adults exhibited lower muscle synergy similarity and reduced gait-related IMC and

Amprion and Prema link memory tests to biomarkers

A quick digital memory test and a lab assay for brain disease are teaming up to flag neurodegeneration earlier. Walk into a kitchen, forget why you’re there, laugh it off. Most of us have done it. But some people notice their memory slipping in ways that feel different, then sit a standard cognitive screening and […] The post Amprion and Prema link memory tests to biomarkers appeared first on Longevity.Technology.

Why some people escape Alzheimer’s despite carrying a high-risk gene

Scientists have discovered why some people with a high genetic risk of Alzheimer’s remain mentally sharp into their 80s, uncovering a rare mutation that protects the brain from harmful protein buildup. The findings reveal a potential new way to prevent early brain damage and could pave the way for treatments that mimic this natural defense.

Just 3,000 steps a day may help slow Alzheimer's, scientists find

Walking just 3,000 steps a day could help slow Alzheimer’s-related brain changes, according to new research. Scientists discovered that physical activity was linked to less buildup of harmful tau proteins and nearly half the cognitive and functional decline, even in people already showing early signs of the disease. The strongest benefits appeared at 5,000 to 7,500 daily steps, suggesting that the popular 10,000-step goal may not be necessary.

"Mind-blowing" Alzheimer’s breakthrough: Two hours of sleep restored without clearing brain plaques

Scientists have uncovered an unexpected culprit behind sleep loss in Alzheimer’s disease: overactive immune cells in the brain. By temporarily removing these cells, researchers restored more than two hours of sleep per day in mice, revealing a promising new target for treatment.

Physical exercise: a multi-target strategy for the prevention and treatment of Alzheimer’s disease

Alzheimer’s disease (AD) is a devastating age-related neurodegenerative disease characterized by irreversible cognitive dysfunction and neuronal loss. The complex pathogenesis of AD involves core proteinopathies of amyloid-β (Aβ) and tau, chronic neuroinflammation, and extensive cerebral metabolic disorders, which collectively drive progressive neuronal damage and disease deterioration. Currently, effective disease-modifying drugs for AD are still lacking, and physical exercise has been recognized as a safe and effective non-pharmacological intervention to prevent and alleviate AD pathological progression. Specifically, exercise inhibits abnormal Aβ deposition and tau hyperphosphorylation, suppresses microglial overactivation and sustained neuroinflammatory responses, and remodels cerebral metabolic homeostasis by improving glucose utilization, balancing lactate metabolism, restoring mit

Linking event-related potentials and structural MRI in the aging brain

Aging alters both brain structure and electrophysiology, which can be measured non-invasively by structural magnetic resonance imaging (MRI) and event-related potentials (ERPs). On average, gray matter declines steadily from early adulthood, whereas white matter increases into midlife before declining. With respect to ERPs, the well-established P300 response shows reduced amplitude and delayed latency from early adulthood onward. Few studies test whether structural MRI and ERP measures correlate within the same individuals, and those that do disagree over which tissue tracks which ERP change. While ERP changes are not coupled to structural changes in a fixed manner, atrophy in gray and white matter tissue correlate with ERP response decay, and a clear pattern of structure–function coupling emerges with age. This dynamic in turn is magnified by age and disease. Technological advances are

Fight Aging! Newsletter, October 19th 2026

Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe to the newsletter, please visit: https://www.fightaging.org/newsletter/. To unsubscribe, send email or reply to this email at newsletter@fightaging.org with "unsubscribe" in the subject or body. Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out more: https://www.fightaging.org/services/ Contents Age-Related Decline in Chaperone-Mediated Autophagy Impairs Clearance of Senescence Cells A Review of Differences Identified in Gu

Brain cells meant to protect us may be fueling cognitive decline

Scientists have uncovered a surprising cause of age-related cognitive decline involving brain cells previously thought to be entirely beneficial. As these cells become dysfunctional, they can produce abnormal amounts of myelin, disrupting nerve fibers and potentially contributing to worsening memory and thinking skills.