Dietary Branched Chain Amino Acids Modify Post-Infarct Cardiac Remodeling and Function in the Murine Heart.

Introduction: Branch-chain amino acids (BCAA) are markedly elevated in the heart following myocardial infarction (MI) in both humans and animal models. Nevertheless, it remains unclear whether dietary BCAA levels influence post-MI remodeling. We hypothesize that lowering dietary BCAA levels prevents adverse cardiac remodeling after MI. Methods and Results: To assess whether altering dietary BCAA levels would impact circulating BCAA concentrations, mice were fed a low (1/3×), normal (1×), or high (2×) BCAA diet over a 7-day period. We found that mice fed the low BCAA diet had >2-fold lower circulating BCAA concentrations when compared with normal and high BCAA diet feeding strategies; notably, the high BCAA diet did not further increase BCAA levels over the normal chow diet. To investigate the impact of dietary BCAAs on cardiac remodeling and function after MI, male and female mice were fed either the low or high BCAA diet for 2 wk prior to MI and for 4 wk after MI. Although body weights or heart masses were not different in female mice fed the custom diets, male mice fed the high BCAA diet had significantly higher body and heart masses than those on the low BCAA diet. Echocardiographic assessments revealed that the low BCAA diet preserved stroke volume and cardiac output for the duration of the study, while the high BCAA diet led to progressive decreases in cardiac function. Although no discernible differences in cardiac fibrosis, scar collagen topography, or cardiomyocyte cross-sectional area were found between the dietary groups, male mice fed the high BCAA diet showed longer cardiomyocytes and higher capillary density compared with the low BCAA group. Conclusions: Provision of a diet low in BCAAs to mice mitigates eccentric cardiomyocyte remodeling and loss of cardiac function after MI, with dietary effects more prominent in males.

1-Iodoglycal: A Versatile Intermediate for the Synthesis of d-Glyco Amides and Esters Employing Carbonylative Cross-Coupling Reaction.

In this study, we present the development of two catalytic processes: a Pd-PEPPSI-catalyzed aminocarbonylation and a Pd(OAc)2-Xantphos-catalyzed alkoxycarbonylation of d-glycals, utilizing carbonylative cross-coupling reactions. We explored successfully various types of aromatic amines, as well as alkyl amines and amino acids, to synthesize new d-glycal amides. However, we observed limitations in the reactivity of alkyl and heteroaromatic amines. The processes enabled the synthesis of 20 novel C1-branched glycoamides and 7 new d-gluco esters.

The ecology of giant kelp colonization and its implications for kelp forest restoration.

The success and cost-effectiveness of kelp forest restoration hinges on understanding the colonization ecology of kelps, particularly with respect to dispersal potential, recruitment success, and subsequent establishment. To gain needed insight into these processes we examined spatial patterns and temporal trajectories of the colonization of a large artificial reef by the giant kelp Macrocystis pyrifera. The 151 ha artificial reef complex was constructed in three phases over 21 years, enabling dispersal, recruitment, and subsequent establishment to be examined for a wide range of environmental conditions, dispersal distances, and source population sizes. Natural colonization of all phases of the artificial reef by giant kelp was rapid (within 1 year) and extended across the entire 7-km-long reef complex. Colonization density declined with distance from the nearest source population, but only during the first phase when the distance from the nearest source population was ≤3.5 km. Despite this decline, recruitment on artificial reef modules farthest from the source population was sufficient to produce dense stands of kelp within a couple of years. Experimental outplanting of the artificial reef with laboratory-reared kelp embryos was largely successful but proved unnecessary, as the standing biomass of kelp resulting from natural recruitment exceeded that observed on nearby natural reefs within 2-3 years of artificial reef construction for all three phases. Such high potential for natural colonization following disturbance has important implications for kelp forest restoration efforts that employ costly and logistically difficult methods to mimic this process by active seeding and transplanting.

Contrasting Disease Progression, Microglia Reactivity, Tolerance, and Resistance to Toxoplasma gondii Infection in Two Mouse Strains.

Our study investigated the innate immune response to Toxoplasma gondii infection by assessing microglial phenotypic changes and sickness behavior as inflammatory response markers post-ocular tachyzoite instillation. Disease progression in Swiss albino mice was compared with the previously documented outcomes in BALB/c mice using an identical ocular route and parasite burden (2 × 105 tachyzoites), with saline as the control. Contrary to expectations, the Swiss albino mice displayed rapid, lethal disease progression, marked by pronounced sickness behaviors and mortality within 11-12 days post-infection, while the survivors exhibited no apparent signs of infection. Comparative analysis revealed the T. gondii-infected BALB/c mice exhibited reduced avoidance of feline odors, while the infected Swiss albino mice showed enhanced avoidance responses. There was an important increase in microglial cells in the dentate gyrus molecular layer of the infected Swiss albino mice compared to the BALB/c mice and their respective controls. Hierarchical cluster and discriminant analyses identified three microglial morphological clusters, differentially affected by T. gondii infection across strains. The BALB/c mice exhibited increased microglial branching and complexity, while the Swiss albino mice showed reduced shrunken microglial arbors, diminishing their morphological complexity. These findings highlight strain-specific differences in disease progression and inflammatory regulation, indicating lineage-specific mechanisms in inflammatory responses, tolerance, and resistance. Understanding these elements is critical in devising control measures for toxoplasmosis.

Timeliness of Childhood Vaccinations Following Strengthening of the Second Year of Life (2YL) Immunization Platform and Introduction of Catch-Up Vaccination Policy in Ghana.

Strengthening routine immunization systems to successfully deliver childhood vaccines during the second year of life (2YL) is critical for vaccine-preventable disease control. In Ghana, the 18-month visit provides opportunities to deliver the second dose of the measles-rubella vaccine (MR2) and for healthcare workers to assess for and provide children with any missed vaccine doses. In 2016, the Ghana Health Service (GHS) revised its national immunization policies to include guidelines for catch-up vaccinations. This study assessed the change in the timely receipt of vaccinations per Ghana's Expanded Program on Immunizations (EPI) schedule, an important indicator of service quality, following the introduction of the catch-up policy and implementation of a multifaceted intervention package. Vaccination coverage was assessed from household surveys conducted in the Greater Accra, Northern, and Volta regions for 392 and 931 children aged 24-35 months with documented immunization history in 2016 and 2020, respectively. Age at receipt of childhood vaccines was compared to the recommended age, as per the EPI schedule. Cumulative days under-vaccinated during the first 24 months of life for each recommended dose were assessed. Multivariable Cox regression was used to assess the associations between child and caregiver characteristics and time to MR2 vaccination. From 2016 to 2020, the proportion of children receiving all recommended doses on schedule generally improved, the duration of under-vaccination was shortened for most doses, and higher coverage rates were achieved at earlier ages for the MR series. More timely infant doses and caregiver awareness of the 2YL visit were positively associated with MR2 vaccination. Fostering a well-supported cadre of vaccinators, building community demand for 2YL vaccination, sustaining service utilization through strengthened defaulter tracking and caregiver-reminder systems, and creating a favorable policy environment that promotes vaccination over the life course are critical to improving the timeliness of childhood vaccinations.

Osteopontin: A novel marker of pre-symptomatic sporadic Alzheimer's disease.

INTRODUCTION: We investigate the role of osteopontin (OPN) in participants with Pre-symptomatic Alzheimer's disease (AD), mild cognitive impairment (MCI), and in AD brains. METHODS: Cerebrospinal fluid (CSF) OPN, AD, and synaptic biomarker levels were measured in 109 cognitively unimpaired (CU), parental-history positive Pre-symptomatic Evaluation of Experimental or Novel Treatments for Alzheimer's Disease (PREVENT-AD) participants, and in 167 CU and 399 participants with MCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. OPN levels were examined as a function of amyloid beta (Aß) and tau positivity. Survival analyses investigated the link between OPN and rate of conversion to AD. RESULTS: In PREVENT-AD, CSF OPN was positively correlated with synaptic biomarkers. In PREVENT-AD and ADNI, OPN was elevated in CSF Aß42/40(+)/total tau(+) and CSF Aß42/40(+)/phosphorylated tau181(+) individuals. In ADNI, OPN was increased in Aß(+) positron emission tomography (PET) and tau(+) PET individuals, and associated with an accelerated rate of conversion to AD. OPN was elevated in autopsy-confirmed AD brains. DISCUSSION: Strong associations between CSF OPN and key markers of AD pathophysiology suggest a significant role for OPN in tau neurobiology, particularly in the early stages of the disease. HIGHLIGHTS: In the Pre-symptomatic Evaluation of Experimental or Novel Treatments for Alzheimer's Disease cohort, we discovered that cerebrospinal fluid (CSF) osteopontin (OPN) levels can indicate early synaptic dysfunction, tau deposition, and neuronal loss in cognitively unimpaired elderly with a parental history. CSF OPN is elevated in amyloid beta(+) positron emission tomography (PET) and tau(+) PET individuals. Elevated CSF OPN is associated with an accelerated rate of conversion to Alzheimer's disease (AD). Elevated CSF OPN is associated with an accelerated rate of cognitive decline on the Alzheimer's Disease Assessment Scale-Cognitive subscale 13, Montreal Cognitive Assessment, Mini-Mental State Examination, and Clinical Dementia Rating Scale Sum of Boxes. OPN mRNA and protein levels are significantly upregulated in the frontal cortex of autopsy-confirmed AD brains.

Capacitive Sensors Based on Recycled Carbon Fibre (rCF) Composites.

Recycled carbon fibre (rCF) composites are increasingly being explored for applications such as strain sensing, manufacturing of automobile parts, assistive technologies, and structural health monitoring due to their properties and economic and environmental benefits. The high conductivity of carbon and its wide application for sensing makes rCF very attractive for integrating sensing into passive structures. In this paper, capacitive sensors have been fabricated using rCF composites of varying compositions. First, we investigated the suitability of recycled carbon fibre polymer composites for different sensing applications. As a proof of concept, we fabricated five touch/proximity sensors and three soil moisture sensors, using recycled carbon fibre composites and their performances compared. The soil moisture sensors were realised using rCF as electrodes. This makes them corrosion-resistant and more environmental-friendly, compared to conventional soil moisture sensors realised using metallic electrodes. The results of the touch/proximity sensing show an average change in capacitance (ΔC/C~34) for 20 mm and (ΔC/C~5) for 100 mm, distances of a hand from the active sensing region. The results of the soil moisture sensors show a stable and repeatable response, with a high sensitivity of ~116 pF/mL of water in the linear region. These results demonstrate their respective potential for touch/proximity sensing, as well as smart and sustainable agriculture.

Safety Assessment of Methylxanthines as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of three methylxanthines, Caffeine, Theobromine, and Theophylline, as used in cosmetics. All of these ingredients are reported to function as skin-conditioning agents in cosmetic products. The Panel reviewed the data relevant to the safety of these ingredients and concluded that Caffeine, Theobromine, and Theophylline are safe in cosmetics in the present practices of use and concentration described in this safety assessment.

Trends in memory function and memory impairment among older adults in the USA and Europe, 1996-2018.

BACKGROUND: Single-country studies document varying time trends in memory function and impairment. Comparative analyses are limited. METHODS: We used self-respondent data on adults aged 50+ years in 13 countries from three surveys (USA: HRS, 1998-2018; England: ELSA, 2002-2018; 11 European countries: SHARE, 2004-2019). Memory is measured with tests of immediate and delayed word recall. Unweighted age- and gender-adjusted mixed effects regression models as well as models with adjustments for additional socio-demographic characteristics and health behaviors were examined. Heterogeneity in trends by gender, age group, and educational attainment were measured. RESULTS: The age-adjusted 10-year improvement in average test score is 0.04 standard deviations (SDs) (95% confidence interval (CI): 0.03, 0.05) in the USA, 0.17 SDs (95% CI: 0.15, 0.19) in England, and 0.24 SDs (95% CI: 0.23, 0.25) in SHARE countries. Trends are largely similar across gender, age groups, and educational attainment. Regional differences in trends remain after adjustment for potential mechanisms. Difference between the USA and other countries is particularly large under aged 75 years compared to over aged 75 years. CONCLUSIONS: Pace of improvement in memory function varies strongly across countries. On average, the 11 European countries studied had the fastest improvement, followed by England. The trend in the USA indicates improvement, but at a much slower pace compared to that in England and other European countries. Uncovering the causes for the cross-country heterogeneity in time trends, and in particular the reasons for the comparatively poor performance of the USA, should be both a research and public health priority.

Potentiation of BKCa channels by cystic fibrosis transmembrane conductance regulator (CFTR) correctors VX-445 and VX-121.

Cystic fibrosis (CF) results from mutations in the CFTR anion channel, ultimately leading to diminished transepithelial anion secretion and mucociliary clearance. CFTR correctors are therapeutics that restore the folding/trafficking of mutated CFTR to the plasma membrane. The BKCa potassium channel is also critical for maintaining lung ASL volume. Here, we show the CFTR corrector, VX-445 (Elexacaftor), a component of Trikafta, induces K+ secretion across WT and F508del CFTR primary human bronchial epithelial cells (HBEs), which was entirely inhibited by the BKCa antagonist paxilline. Similar results were observed with VX-121 - a corrector under clinical evaluation. Whole-cell patch-clamp recordings confirmed potentiated channel activity from CFTR correctors on the BKCa α-subunit, and excised patch-clamp recordings demonstrated a significant increase in open probability. In mesenteric artery, VX-445 induced a paxilline-sensitive vasorelaxation of preconstricted arteries. VX-445 also reduced action potential firing frequency in primary hippocampal and cortical neurons. VX-445 effects were observed at low micomolar concentrations (1-10 µM) - within the range reported in plasma and tissues from CF patients. We raise the possibilities that CFTR correctors gain additional clinical benefit by activation of BKCa in the lung, yet may lead to adverse events through BKCa activation, elsewhere.

Prosapia bicincta (Hemiptera: Cercopidae) abundance, plant associations, and impacts on groundcover in Hawai'i Island rangelands.

The twolined spittlebug, Prosapia bicincta (Say), is a major economic pest of forage grass and turfgrass. Prosapia bicincta was first detected in rangelands on Hawai'i Island in 2016 and has since spread to an estimated 72,000 ha in the North and South Kona districts. This study aimed to quantify P. bicincta abundance, plant associations, and impacts on groundcover over time. Monthly surveys of P. bicincta nymphs and adults were conducted from February 2018 to September 2022 along 17 established 100-m transects at 4 ranches located in Kona, Hawai'i Island, spanning an elevation gradient from 519 to 1,874 m above sea level (a.s.l.). Monitoring revealed P. bicincta occurs from 519 to 1,679 m a.s.l., primarily in Kikuyu grass (Cenchrus clandestinus (Hochst. ex Chiov.)) Morrone (Poales: Poaceae) pastures. Peaks in P. bicincta abundance coincided with the wet season, with most activity occurring from April to October and little to no activity between November and March. Mid elevation (1,000-1,300 m) transects had significantly higher mean P. bicincta abundance (126 nymphs/m2) relative to low (500-999 m) (64 nymphs/m2) and high elevations (>1,300 m) (20 nymphs/m2). Sites with the highest abundance of P. bicincta were also associated with the greatest decrease in mean grass cover (30%) and were replaced by forbs, bare ground, and shrubs. Grasses accounted for 72% of the total P. bicincta detections, with the remaining plants comprised of legumes (16%), sedges (6%), and forbs (6%). Twenty new P. bicincta plant associations were found. This information will help improve the effectiveness of management to suppress populations below economic thresholds.

Combining multimodal connectivity information improves modelling of pathology spread in Alzheimer's disease.

Cortical atrophy and aggregates of misfolded tau proteins are key hallmarks of Alzheimer's disease. Computational models that simulate the propagation of pathogens between connected brain regions have been used to elucidate mechanistic information about the spread of these disease biomarkers, such as disease epicentres and spreading rates. However, the connectomes that are used as substrates for these models are known to contain modality-specific false positive and false negative connections, influenced by the biases inherent to the different methods for estimating connections in the brain. In this work, we compare five types of connectomes for modelling both tau and atrophy patterns with the network diffusion model, which are validated against tau PET and structural MRI data from individuals with either mild cognitive impairment or dementia. We then test the hypothesis that a joint connectome, with combined information from different modalities, provides an improved substrate for the model. We find that a combination of multimodal information helps the model to capture observed patterns of tau deposition and atrophy better than any single modality. This is validated with data from independent datasets. Overall, our findings suggest that combining connectivity measures into a single connectome can mitigate some of the biases inherent to each modality and facilitate more accurate models of pathology spread, thus aiding our ability to understand disease mechanisms, and providing insight into the complementary information contained in different measures of brain connectivity.

TIN-X version 3: update with expanded dataset and modernized architecture for enhanced illumination of understudied targets.

TIN-X (Target Importance and Novelty eXplorer) is an interactive visualization tool for illuminating associations between diseases and potential drug targets and is publicly available at newdrugtargets.org. TIN-X uses natural language processing to identify disease and protein mentions within PubMed content using previously published tools for named entity recognition (NER) of gene/protein and disease names. Target data is obtained from the Target Central Resource Database (TCRD). Two important metrics, novelty and importance, are computed from this data and when plotted as log(importance) vs. log(novelty), aid the user in visually exploring the novelty of drug targets and their associated importance to diseases. TIN-X Version 3.0 has been significantly improved with an expanded dataset, modernized architecture including a REST API, and an improved user interface (UI). The dataset has been expanded to include not only PubMed publication titles and abstracts, but also full-text articles when available. This results in approximately 9-fold more target/disease associations compared to previous versions of TIN-X. Additionally, the TIN-X database containing this expanded dataset is now hosted in the cloud via Amazon RDS. Recent enhancements to the UI focuses on making it more intuitive for users to find diseases or drug targets of interest while providing a new, sortable table-view mode to accompany the existing plot-view mode. UI improvements also help the user browse the associated PubMed publications to explore and understand the basis of TIN-X's predicted association between a specific disease and a target of interest. While implementing these upgrades, computational resources are balanced between the webserver and the user's web browser to achieve adequate performance while accommodating the expanded dataset. Together, these advances aim to extend the duration that users can benefit from TIN-X while providing both an expanded dataset and new features that researchers can use to better illuminate understudied proteins.

Single-nucleus multi-omics of Parkinson's disease reveals a glutamatergic neuronal subtype susceptible to gene dysregulation via alteration of transcriptional networks.

The genetic architecture of Parkinson's disease (PD) is complex and multiple brain cell subtypes are involved in the neuropathological progression of the disease. Here we aimed to advance our understanding of PD genetic complexity at a cell subtype precision level. Using parallel single-nucleus (sn)RNA-seq and snATAC-seq analyses we simultaneously profiled the transcriptomic and chromatin accessibility landscapes in temporal cortex tissues from 12 PD compared to 12 control subjects at a granular single cell resolution. An integrative bioinformatic pipeline was developed and applied for the analyses of these snMulti-omics datasets. The results identified a subpopulation of cortical glutamatergic excitatory neurons with remarkably altered gene expression in PD, including differentially-expressed genes within PD risk loci identified in genome-wide association studies (GWAS). This was the only neuronal subtype showing significant and robust overexpression of SNCA. Further characterization of this neuronal-subpopulation showed upregulation of specific pathways related to axon guidance, neurite outgrowth and post-synaptic structure, and downregulated pathways involved in presynaptic organization and calcium response. Additionally, we characterized the roles of three molecular mechanisms in governing PD-associated cell subtype-specific dysregulation of gene expression: (1) changes in cis-regulatory element accessibility to transcriptional machinery; (2) changes in the abundance of master transcriptional regulators, including YY1, SP3, and KLF16; (3) candidate regulatory variants in high linkage disequilibrium with PD-GWAS genomic variants impacting transcription factor binding affinities. To our knowledge, this study is the first and the most comprehensive interrogation of the multi-omics landscape of PD at a cell-subtype resolution. Our findings provide new insights into a precise glutamatergic neuronal cell subtype, causal genes, and non-coding regulatory variants underlying the neuropathological progression of PD, paving the way for the development of cell- and gene-targeted therapeutics to halt disease progression as well as genetic biomarkers for early preclinical diagnosis.

Safety Assessment of Polyol Phosphates as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of 10 polyol phosphates. Some of the possible functions in cosmetics that are reported for this ingredient group are chelating agents, oral care agents, and skin conditioning agents. The Panel reviewed relevant data relating to the safety of these ingredients under the intended conditions of use in cosmetic formulations, and concluded that Sodium Phytate, Phytic Acid, Phytin, and Trisodium Inositol Triphosphate are safe in cosmetics in the present practices of use and concentration described in the safety assessment. The Panel also concluded that the data are insufficient to determine the safety of the following 6 ingredients as used in cosmetics: Disodium Glucose Phosphate, Manganese Fructose Diphosphate, Sodium Mannose Phosphate, Trisodium Fructose Diphosphate, Xylityl Phosphate, and Zinc Fructose Diphosphate.

Extrinsic Positive End-Expiratory Pressure due to Failure of the Positive-Pressure Relief Valve Within the Scavenging System: A Case Report.

The anesthesia gas scavenging system (AGSS) removes waste gases from the anesthesia machine. Within the AGSS, safety features prevent excessive pressures from affecting ventilation. Although the literature contains reports describing failures of the AGSS, we found no reports of positive-pressure relief valve (PPRV) malfunctions. We encountered 2 cases of extrinsic positive end-expiratory pressure (PEEP) resulting from a malfunctioning PPRV. Both cases suffered delayed identification intraoperatively but patients did not experience postoperative complications. These cases highlight the importance of daily scavenger system prechecks, the potential physiologic implications of AGSS malfunctions, and the importance of preplanned contingencies for machine failure.

Brain Networks, Neurotransmitters and Psychedelics: Towards a Neurochemistry of Self-Awareness.

PURPOSE OF REVIEW: Self-awareness can be defined as the capacity of becoming the object of one's own awareness and, increasingly, it has been the target of scientific inquiry. Self-awareness has important clinical implications, and a better understanding of the neurochemical basis of self-awareness may help clarifying causes and developing interventions for different psychopathological conditions. The current article explores the relationship between neurochemistry and self-awareness, with special attention to the effects of psychedelics. RECENT FINDINGS: The functioning of self-related networks, such as the default-mode network and the salience network, and how these are influenced by different neurotransmitters is discussed. The impact of psychedelics on self-awareness is reviewed in relation to specific processes, such as interoception, body ownership, agency, metacognition, emotional regulation and autobiographical memory, within a framework based on predictive coding. Improved outcomes in emotional regulation and autobiographical memory have been observed in association with the use of psychedelics, suggesting higher-order self-awareness changes, which can be modulated by relaxation of priors and improved coping mechanisms linked to cognitive flexibility. Alterations in bodily self-awareness are less consistent, being potentially impacted by doses employed, differences in acute/long-term effects and the presence of clinical conditions. Future studies investigating the effects of different molecules in rebalancing connectivity between resting-state networks may lead to novel therapeutic approaches and the refinement of existing treatments.

Identification of retinal oligomeric, citrullinated, and other tau isoforms in early and advanced AD and relations to disease status.

This study investigates various pathological tau isoforms in the retina of individuals with early and advanced Alzheimer's disease (AD), exploring their connection with disease status. Retinal cross-sections from predefined superior-temporal and inferior-temporal subregions and corresponding brains from neuropathologically confirmed AD patients with a clinical diagnosis of either mild cognitive impairment (MCI) or dementia (n = 45) were compared with retinas from age- and sex-matched individuals with normal cognition (n = 30) and non-AD dementia (n = 4). Retinal tau isoforms, including tau tangles, paired helical filament of tau (PHF-tau), oligomeric-tau (Oligo-tau), hyperphosphorylated-tau (p-tau), and citrullinated-tau (Cit-tau), were stereologically analyzed by immunohistochemistry and Nanostring GeoMx digital spatial profiling, and correlated with clinical and neuropathological outcomes. Our data indicated significant increases in various AD-related pretangle tau isoforms, especially p-tau (AT8, 2.9-fold, pS396-tau, 2.6-fold), Cit-tau at arginine residue 209 (CitR209-tau; 4.1-fold), and Oligo-tau (T22+, 9.2-fold), as well as pretangle and mature tau tangle forms like MC-1-positive (1.8-fold) and PHF-tau (2.3-fold), in AD compared to control retinas. MCI retinas also exhibited substantial increases in Oligo-tau (5.2-fold), CitR209-tau (3.5-fold), and pS396-tau (2.2-fold). Nanostring GeoMx analysis confirmed elevated retinal p-tau at epitopes: Ser214 (2.3-fold), Ser396 (2.6-fold), Ser404 (2.4-fold), and Thr231 (1.8-fold), particularly in MCI patients. Strong associations were found between retinal tau isoforms versus brain pathology and cognitive status: a) retinal Oligo-tau vs. Braak stage, neurofibrillary tangles (NFTs), and CDR cognitive scores (ρ = 0.63-0.71), b) retinal PHF-tau vs. neuropil threads (NTs) and ABC scores (ρ = 0.69-0.71), and c) retinal pS396-tau vs. NTs, NFTs, and ABC scores (ρ = 0.67-0.74). Notably, retinal Oligo-tau strongly correlated with retinal Aß42 and arterial Aß40 forms (r = 0.76-0.86). Overall, this study identifies and quantifies diverse retinal tau isoforms in MCI and AD patients, underscoring their link to brain pathology and cognition. These findings advocate for further exploration of retinal tauopathy biomarkers to facilitate AD detection and monitoring via noninvasive retinal imaging.