Skip to main content

Aggregator

Antibody drug conjugates in Alzheimer's disease: emerging strategies and future directions

1 day 1 hour ago
Antibody-drug conjugates (ADCs) are emerging as a targeted therapeutic strategy for Alzheimer's disease (AD), offering precise delivery of disease modifying agents with reduced systemic toxicity. By linking monoclonal antibodies to small-molecule payloads, ADCs hold promise in overcoming key challenges in AD treatment, including poor blood-brain barrier (BBB) penetration and off-target effects. This review provides a critical synthesis of ADC strategies in neurodegeneration, with emphasis on...
Mandana AmeliMojarad

Complexity of olfactory-evoked EEG as an evidence-based marker of Alzheimer's disease

1 day 1 hour ago
Olfactory impairment is an early symptom of Alzheimer's disease (AD). However, currently used olfactory task-based functional magnetic resonance imaging (fMRI), functional near-infrared spectroscopy (fNIRS), and electroencephalogram features are not powerful enough to detect the impairment. To address this issue, we propose an explainable Artificial Intelligence (XAI) framework that comprises discriminant analysis/naive Bayes/thresholding classifiers driven by the sample entropy (SE) of...
Justin Joseph

The Rise and Deceleration of Neuronal Excitability in Aging and Alzheimer's Disease: Mechanisms, Implications, and Therapeutic Targets

1 day 1 hour ago
Neuronal hyperexcitability-defined as increased likelihood of action potential firing in response to stimuli-has emerged as a key pathophysiological feature in both normal aging and Alzheimer's disease (AD). This review synthesizes current evidence across species and models, evaluating the prevalence, mechanisms, and consequences of heightened excitability at the cellular and network levels. We examine electrophysiological and imaging-based indicators of hyperexcitability, including enhanced...
Osvaldo Delbono

Multidimensional plasticity of natural killer cells in tumours

1 day 1 hour ago
Natural killer (NK) cells exhibit remarkable adaptability within the tumour microenvironment (TME), where dynamic shifts in phenotype, function and metabolism govern their dual roles in antitumour immunity and tumour immune evasion. In the TME, NK cells undergo receptor remodelling, which is characterised by upregulated inhibitory signals and suppressed activating receptors, leading to the formation of dysfunctional subsets, such as exhausted TIM-3⁺ NK cells or tissue-resident CD49a⁺...
Xinya Yang

Targeting intrinsically disordered nuclear protein 1 (NUPR1) with single-domain antibodies alleviates triple-negative breast cancer (TNBC) progression in vivo

1 day 1 hour ago
Triple-negative breast cancer (TNBC) is a highly aggressive subtype that currently lacks effective targeted therapies. Transcriptional co-regulator nuclear protein 1 (NUPR1) has been identified as a key stress-adaptive disordered protein that promotes tumor progression and therapy-induced resistance. In this study, we developed a robust high-throughput platform integrating in situ proximity ligation assay followed by DNA sequencing (isPLA-seq), NanoBiT assays, and C-degron degradation validation...
Tianzhuo Wang

The Rise and Deceleration of Neuronal Excitability in Aging and Alzheimer's Disease: Mechanisms, Implications, and Therapeutic Targets

1 day 1 hour ago
Neuronal hyperexcitability-defined as increased likelihood of action potential firing in response to stimuli-has emerged as a key pathophysiological feature in both normal aging and Alzheimer's disease (AD). This review synthesizes current evidence across species and models, evaluating the prevalence, mechanisms, and consequences of heightened excitability at the cellular and network levels. We examine electrophysiological and imaging-based indicators of hyperexcitability, including enhanced...
Osvaldo Delbono

Aducanumab binding to Aβ<sub>1-42</sub> fibrils alters dynamics of the N-terminal tail while preserving the fibril core

1 day 1 hour ago
Aducanumab, a human IgG1 antibody with plaque-clearing effects and modest clinical benefit, binds selectively to aggregated Aβ via the N-terminal region. Yet, the molecular details of how the antibody engages Aβ(1-42) fibrils remain unresolved. Using magic-angle spinning NMR, we show that binding of aducanumab preserves the overall architecture of the Aβ(1-42) fibril core while inducing significant structural and dynamic perturbations in the N-terminal region. Antibody binding markedly reduces...
Ravi Shankar Palani

Targeted gene transfer into developmentally defined cell populations of the primate brain

1 day 1 hour ago
The primate brain possesses unique physiological and developmental features, yet its systematic investigation has been hampered by a paucity of transgenic germline models and tools. Here, we present a minimally invasive method to introduce transgenes widely across the primate cerebral cortex using ultrasound-guided fetal intracerebroventricular viral injections (FIVIs). FIVI enables efficient and long-lasting transgene expression following intrauterine delivery of recombinant adeno-associated...
Ana Rita Ribeiro Gomes

Antibiotic-induced microbiota depletion impairs the proregenerative response to a biological scaffold

1 day 1 hour ago
Therapeutic biological scaffolds promote tissue repair primarily through the induction of type 2 immunity. However, systemic immunological factors, including aging, sex, and previous infections, can modulate this response. The gut microbiota is a well-established modulator of immune function across organ systems, yet its influence on type 2-mediated repair remains underexplored. Here, we establish a bidirectional relationship between the gut microbiota and biological scaffold-mediated tissue...
Natalie Rutkowski

Assessing neurocognitive functioning among adults ageing with and without HIV at the Kenyan Coast: measurement issues and correlates

1 day 1 hour ago
CONCLUSION: We demonstrated the feasibility of OCSPlus administration by trained lay persons, its acceptability, and preliminary reliability and validity among low-literacy older adults on the Kenyan coast. Mean cognitive scores were mixed across the two groups. Cognitive performance was associated with several biopsychosocial factors spanning behavioural/lifestyle, sociodemographic, psychosocial, medical and treatment factors. Further validation studies and epidemiological research are needed...
Patrick N Mwangala

Machine learning-based early screening of mild cognitive impairment using nutrition-related biomarkers and functional indicators

1 day 1 hour ago
CONCLUSION: TMAO-related metabolites consistently contributed positive SHAP effects, suggesting biologically relevant links between dietary metabolism and early cognitive decline. This interpretable ML framework offers a feasible, sensitive, and biologically informed approach for early MCI screening and supports the integration of nutritional biomarkers into cognitive health surveillance.
Ling Yuan

Transcranial alternating current stimulation improves ballistic motor performance in trained and untrained limbs of healthy older adults

1 day 1 hour ago
Transcranial alternating current stimulation (tACS) using a combined theta-gamma waveform can improve unilateral ballistic motor performance in the trained limb of older adults. The purpose of this study was to examine the effect of individual (theta) and combined (theta-gamma) tACS waveforms on ballistic motor performance in the trained and untrained contralateral limb (i.e. cross-limb transfer) of older adults. Sixty right-handed healthy older adults (68.9 ± 5.2 years) received either...
Nishadi N Gamage

CD47 signaling in aging and age-related diseases: mechanisms, challenges, and therapeutic opportunities

1 day 1 hour ago
Aging is marked by progressive dysfunction in cellular maintenance pathways, including mitochondrial impairment, reduced autophagic capacity, and accumulation of senescent cells, which contribute to chronic low-grade inflammation. The transmembrane protein CD47 best known for delivering a "don't eat me" signal through SIRPα is increasingly recognized as an important modulator of several aging-related processes. Its upregulation in aged or inflamed tissues can inhibit the clearance of damaged or...
Arsene Mutombo Menga