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

3 weeks 3 days 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

3 weeks 3 days 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

3 weeks 3 days 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

3 weeks 3 days 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

3 weeks 3 days 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

3 weeks 3 days 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

3 weeks 3 days 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

Longitudinal brain-wide recordings reveal early neurophysiological alterations in memory-impaired mice

3 weeks 4 days ago
Scopolamine, a muscarinic receptor antagonist, is widely utilized to pharmacologically model Alzheimer's disease (AD) due to its ability to mimic cholinergic deficits and induce memory impairments. Despite its common use in investigating behavioral and cognitive impairments in memory deficit animal models, the longitudinal brain-wide electrophysiological alterations associated with scopolamine administration remain largely unexplored. This study integrated electrophysiological and behavioral...
Abdelrahman B M Eldaly

Therapeutic effects of Total flavonoids of Epimedium Folium on sarcopenia via modulation of gut microbiota and bile acid metabolism

3 weeks 4 days ago
CONCLUSIONS: In the present study, TFE was shown to improve dexamethasone-induced muscle atrophy and degeneration in C2C12 myotubes, as evidenced by the restored expression of myogenic markers and the downregulation of atrophy-related genes and proteins. Additionally, TFE can attenuate sarcopenia progression in SAMP8 mice. Its effect was related to the regulation of the gut microbiota-bile acids-skeletal muscle axis.
Yujie Zhang

D-galactose administration via semicircular canal induces accelerated cochlear aging: A novel model of oxidative stress-mediated presbycusis

3 weeks 4 days ago
Age-related hearing loss (ARHL) is a progressive, bilateral sensorineural impairment with significant socio-psychological consequences. Current ARHL models (natural aging or systemic D-galactose (D-gal) injection) face limitations: prolonged timelines, high variability, and inconsistent D-gal protocols. To concentrate aging pathology within the peripheral auditory system, we developed a novel accelerated cochlear aging model by targeted delivery of D-gal via the posterior semicircular canal....
Chunli Zhao

Infectious diseases, infection control, vaccines and long-term care: an European interdisciplinary Council on ageing consensus document

3 weeks 4 days ago
The accelerating ageing of populations worldwide presents profound challenges for public health, particularly within long-term care facilities (LTCFs). Older adults, often burdened by multimorbidity, frailty, and immunosenescence, are highly vulnerable to vaccine-preventable diseases such as influenza, pneumococcal pneumonia, COVID-19, respiratory syncytial virus (RSV), pertussis, and herpes zoster (HZ). Despite the availability of effective vaccines, immunization coverage in LTCFs remains...
Nicola Veronese