The plasma miRNAome in ADNI: Signatures to aid the detection of at‐risk individuals

Alzheimer s & Dementia, Год журнала: 2024, Номер 20(11), С. 7479 - 7494

Опубликована: Сен. 18, 2024

Abstract INTRODUCTION MicroRNAs are short non‐coding RNAs that control proteostasis at the systems level and emerging as potential prognostic diagnostic biomarkers for Alzheimer's disease (AD). METHODS We performed small RNA sequencing on plasma samples from 847 Disease Neuroimaging Initiative (ADNI) participants. RESULTS identified microRNA signatures correlate with AD diagnoses help predict conversion mild cognitive impairment (MCI) to AD. DISCUSSION Our data demonstrate can be used not only diagnose MCI, but also, critically, MCI Moreover, combined neuropsychological testing, microRNAome evaluation helps conversion. These findings of considerable public interest because they provide a path toward reducing indiscriminate utilization costly invasive testing by defining at‐risk segment aging population. Highlights first analysis ADNI study. The levels several microRNAs prediction Adding in clinical setting increases accuracy prediction.

Язык: Английский

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Counterfactual MRI Generation with Denoising Diffusion Models for Interpretable Alzheimer’s Disease Effect Detection

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 8, 2024

Abstract Generative AI models have recently achieved mainstream attention with the advent of powerful approaches such as stable diffusion, DALL-E and MidJourney. The underlying breakthrough generative mechanism denoising diffusion modeling can generate high quality synthetic images learn distribution complex, high-dimensional data. Recent research has begun to extend these medical specifically neuroimaging Typical tasks diagnostic classification predictive often rely on deep learning based convolutional neural networks (CNNs) vision transformers (ViTs), additional steps help in interpreting results. In our paper, we train conditional latent (LDM) probabilistic (DDPM) provide insight into Alzheimer’s disease (AD) effects brain’s anatomy at individual level. We first created that could MRIs, by training them real 3D T1-weighted MRI scans, conditioning process clinical diagnosis a context variable. conducted experiments overcome limitations dataset size, compute time memory resources, testing different model sizes, pretraining, duration, models. tested sampling disease-conditioned using metrics assess realism diversity generated MRIs. also evaluated ability conditionally sample brains CNN-based classifier relative experiments, data helped an AD (using only 500 scans) -and boosted its performance over 3% when scans. Further, used implicit classifier-free guidance alter encoded scan counterfactual (representing healthy subject same age sex) while preserving subject-specific image details. From this (where person appears healthy), personalized map was identify possible brain. Our approach efficiently generates realistic diverse data, may create interpretable AI-based maps for neuroscience applications.

Язык: Английский

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Neuronal cathepsin S increases neuroinflammation and causes cognitive decline via CX3CL1‐CX3CR1 axis and JAK2‐STAT3 pathway in aging and Alzheimer's disease

Aging Cell, Год журнала: 2024, Номер unknown

Опубликована: Окт. 25, 2024

Abstract Aging is an intricate process involving interactions among multiple factors, which one of the main risks for chronic diseases, including Alzheimer's disease (AD). As a member cysteine protease, cathepsin S (CTSS) has been implicated in inflammation across various diseases. Here, we investigated role neuronal CTSS aging and AD started by examining expression hippocampus neurons mice identified significant increase, was negatively correlated with recognition abilities. Concurrently, observed elevation concentration serum elderly people. Transcriptome fluorescence‐activated cell sorting (FACS) results revealed that overexpression aggravated brain inflammatory milieu microglia activation to M1 pro‐inflammatory phenotype, chemokine C‐X3‐C‐motif ligand 1 (CX3CL1)—chemokine receptor (CX3CR1) axis janus kinase 2 (JAK2)—signal transducer activator transcription 3 (STAT3) pathway. CX3CL1 secreted acts on CX3CR1 microglia, our first time neuron neuron–microglia “crosstalk.” Besides, elevated regions patients, hippocampus. Utilizing selective inhibitor, LY3000328, rescued AD‐related pathological features APP/PS1 mice. We further noticed increased B (CTSB) activity, but decreased L (CTSL) activity microglia. Overall, provide evidence can be used as biomarker plays regulatory roles through modulating neuroinflammation process.

Язык: Английский

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Neuroimaging in Dementia

CONTINUUM Lifelong Learning in Neurology, Год журнала: 2024, Номер 30(6), С. 1761 - 1789

Опубликована: Дек. 1, 2024

ABSTRACT OBJECTIVE This article captures the current literature regarding use of neuroimaging measures to study neurodegenerative diseases, including early- and late-onset Alzheimer disease, vascular cognitive impairment, frontotemporal lobar degeneration disorders, dementia with Lewy bodies, Parkinson disease dementia. In particular, highlights significant recent changes in novel therapeutics now available for treatment defining using biological frameworks. Studies summarized include those structural functional MRI (fMRI) techniques, as well metabolic molecular emission tomography imaging (ie, positron [PET] single-photon computerized [SPECT]). LATEST DEVELOPMENTS Neuroimaging are considered essential biomarkers detection diagnosis most diseases. The approval anti-amyloid antibody therapies has highlighted importance PET techniques eligibility monitoring associated side effects. Given success initial biomarker-based classification system (the amyloid, tau, neurodegeneration [A/T/N] framework), researchers impairment have created similar diagnosis. Further, A/T/N framework been updated several pathologic targets biomarker detection. ESSENTIAL POINTS Neurodegenerative diseases a major health impact on millions patients around world. rapidly becoming diagnostic tools detection, monitoring, educates readers about surrounding along important developments field.

Язык: Английский

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ViT transfer learning for fMRI (VTFF): A highway to achieve superior performance for multi-classification of cognitive decline

Biomedical Signal Processing and Control, Год журнала: 2025, Номер 104, С. 107557 - 107557

Опубликована: Янв. 24, 2025

Язык: Английский

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Dissociable spatial topography of cortical atrophy in early‐onset and late‐onset Alzheimer's disease: A head‐to‐head comparison of the LEADS and ADNI cohorts

Alzheimer s & Dementia, Год журнала: 2025, Номер unknown

Опубликована: Фев. 19, 2025

Abstract INTRODUCTION Early‐onset and late‐onset Alzheimer's disease (EOAD LOAD, respectively) have distinct clinical manifestations, with prior work based on small samples suggesting unique patterns of neurodegeneration. The current study performed a head‐to‐head comparison cortical atrophy in EOAD using two large well‐characterized cohorts (LEADS ADNI). METHODS We analyzed brain structural magnetic resonance imaging (MRI) data acquired from 377 sporadic patients 317 sporadicLOAD who were amyloid positive had mild cognitive impairment (MCI) or dementia (i.e., early‐stage AD), along cognitively unimpaired participants. RESULTS After controlling for the level impairment, we found double dissociation between AD phenotype localization/magnitude atrophy, characterized by predominant neocortical involvement more focal anterior medial temporal LOAD. DISCUSSION Our findings point to utility MRI‐based biomarkers differentiating which may be useful diagnosis, prognostication, treatment. Highlights (EOAD) (LOAD) showed overlapping patterns. prominent widespread regions. LOAD lobe. Regional was correlated severity global impairment. Results comparable when sample stratified dementia.

Язык: Английский

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Technical Assessment of Motor and Behavioral Tests in Rodent Models of Multiple Sclerosis

Journal of Integrative Neuroscience, Год журнала: 2025, Номер 24(2)

Опубликована: Фев. 21, 2025

Background: Multiple sclerosis (MS) is a neurodegenerative disorder characterized by progressive motor and cognitive impairments, affecting millions worldwide. It significantly reduces patients’ quality of life imposes burden on health systems. Despite advances in understanding MS, there no cure, highlighting the need for effective therapeutic strategies. Preclinical animal models are critical gaining insights into MS pathophysiology treatments. However, these fail to fully replicate complexity human making it essential choose appropriate behavioral tests evaluate their efficacy. Purpose: This review examines various used preclinical models, discussing strengths limitations. The goal guide researchers selecting most while providing how performed analyzed. Methods: We reviewed detailing test procedures evaluating advantages disadvantages. Results: offers comprehensive overview that aids choosing suitable studies, improving accuracy reliability research. Conclusions: Understanding limitations crucial informed decisions, leading better experimental designs and, ultimately, more interventions MS.

Язык: Английский

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Factors associated with age at tau pathology onset and time from tau onset to dementia

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

Abstract INTRODUCTION Elevated tau is temporally proximal to dementia onset but less known about factors influencing T+ age and time following in Alzheimer’s disease. We used sampled iterative localized approximation (SILA) estimated (ETOA) investigate associated with from ADNI. METHODS Using SILA-estimated A+ ages derived 18 F-Flortaucipir, F-Florbetapir, F-Florbetaben PET Cox proportional hazards accelerated failure models, we analyzed APOE , sex, amyloid burden, age, educational attainment, literacy associations ETOA dementia. RESULTS Higher amyloid, -ε4, lower education, younger ETOA. Older higher shorter DISCUSSION This work highlights the prognostic value of need better characterize contributing AD.

Язык: Английский

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Detecting short-interval longitudinal cortical atrophy in neurodegenerative dementias via cluster scanning: A proof of concept

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 17, 2025

Abstract Regional brain atrophy estimated from structural magnetic resonance imaging (MRI) is a widely used measure of neurodegeneration in Alzheimer’s disease (AD), Frontotemporal Lobar Degeneration (FTLD), and other dementias. Yet, traditional MRI-derived morphometric estimates are susceptible to measurement errors, posing challenge for reliably detecting longitudinal atrophy, particularly over short intervals. Here, we examined the utility multiple MRI scans acquired rapid succession (i.e., cluster scanning ) cortical 3- 6-month intervals within individual patients. Four individuals with mild cognitive impairment or dementia likely due AD FTLD participated this study. At baseline, 3 months, 6 data were collected on Tesla scanner using fast 1.2-mm T1-weighted multi-echo magnetization-prepared gradient echo (MEMPRAGE) sequence (acquisition time = 2’23’’). each timepoint, participants underwent up 32 MEMPRAGE four separate sessions two days. Using linear mixed-effects models, phenotypically vulnerable (“core atrophy”) regions exhibited statistically significant all decreased thickness) by months further demonstrated preferential vulnerability compared control three at least one 3-month These findings provide proof-of-concept evidence that pooling derived can detect patients neurodegenerative

Язык: Английский

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Optimized 5‐HT_2b inhibitors for neuropsychiatric syndromes with cognitive dysfunction

Alzheimer s & Dementia Translational Research & Clinical Interventions, Год журнала: 2025, Номер 11(1)

Опубликована: Янв. 1, 2025

Язык: Английский

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