NeuroSci

Alzheimer’s disease (AD) is marked by amyloid plaques, hyperphosphorylated TAU proteins, and neuroinflammation. The APP/PS1 mouse model is widely used to study AD pathogenesis. In this study, we investigated the expression of chemokines and their receptors, which may play a role in AD’s pathological mechanisms, using brain cortex tissue from female APP/PS1 mice aged 20–21 months. We analyzed several chemokine receptors (CCR1, CCR2, CCR3, CCR4, CCR6, CCR7, CCR9, and CCR10) by Western blot and focused on CCR6, CCR7, and CCR10 using RT-PCR. Additionally, we quantified the levels of chemokines (CCL6, CCL8, CCL19, CCL20, CCL24, and CCL27) by RT-PCR. Our results showed a significant decrease in CCL8 and CCL19, along with their respective receptors, in the APP/PS1 mice compared to controls. On the other hand, we observed a notable increase in CCL6, CCL24, CCL20, CCL27, and their receptors. Chemokines like CCL8 and CCL20, involved in inflammatory responses, may reveal how neuroinflammation contributes to AD. CCL19 and CCL27 are linked to immune cell trafficking, which may help explain immune cell interactions with amyloid plaques and TAU tangles in the CNS. Overall, the altered expression of chemokines such as CCL24 could serve as biomarkers for early AD detection and monitoring disease progression. These findings suggest potential therapeutic targets to modulate immune responses and reduce neuroinflammation in AD.

Background: Prior SMA mortality studies have shown excess mortality in people with SMA, but the literature lacks data on disparities in SMA-related mortality. This study examined disparities in SMA-related mortality in the United States in the post-treatment era (2018–2023). Methods: This was a population-based study using the CDC Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database. The International Classification of Disease (ICD), 10th Revision, Clinical Modification codes, G12.0, G12.1, G12.8, and G12.9, were used to identify SMA. The data were stratified by biological sex, race/ethnicity (Non-Hispanic/NH White, NH Black, Hispanic, Asian) and Census regions (West, Northeast, Midwest, South). The analysis was conducted by calculating rate ratios (RR) of age-adjusted mortality rate (AAMR). Results: There were 821 (45.8% female) SMA-related deaths across the study period. Males were associated with higher AAMR than females (RR = 1.189, 95% CI: 1.035 to 1.366). The SMA-AAMR for NH White individuals was the highest compared to Hispanic individuals (RR = 1.808, 95% CI: 1.420 to 2.300), followed by NH Black and Asian individuals. The West carried the highest AAMR compared to the Northeast (RR = 1.581, 95% CI: 1.263 to 1.978), followed by the Midwest and the South. The age at death distribution showed a bimodal pattern, as follows: 5–14 years and 65–74 years. The infant age group (<1 year) was associated with the highest AAMR compared to all other age groups. Conclusion: Our findings showed that SMA-related mortality was highest in infants, NH White individuals, the West, and males. These data may assist future efforts to reduce the burden of SMA.

Developmental dyslexia (DD) often involves difficulties in phonological processing of speech. Objectives: While underlying neural changes have been identified in terms of stimulus- and task-related responses within specific brain regions and their neural connectivity, there is still limited understanding of how these changes affect the overall organization of brain networks. Methods: This study used EEG and functional network analysis, focusing on small-world propensity across various frequency bands (from δ to γ), to explore the global brain organization during the auditory discrimination of words and pseudowords in children with DD. Results: The main finding revealed a systemic inefficiency in the functional network of individuals with DD, which did not achieve the optimal small-world propensity. This inefficiency arises from a fundamental trade-off between localized specialization and global communication. During word listening, the δ-/γ1-networks (related to impaired syllabic and phonemic processing of words) and the θ-/β-networks (related to pseudoword listening) in the DD group showed lower local clustering and connectivity compared to the control group, resulting in reduced functional segregation. In particular, the θ-/β-networks for words in the DD group exhibited a less optimal balance between specialized local processing and effective global communication. Centralized midline hubs, such as the postcentral gyrus (PstCG) and inferior frontal gyrus (IFG), which are crucial for global coordination, attention, and executive control, were either absent or inconsistent in individuals with DD. Consequently, the DD network adopted a constrained, motor-compensatory, and left-lateralized strategy. This led to the redirection of information flow and processing effort toward the left PstCG/IFG loop, interpreted as a compensatory effort to counteract automatic processing failures. Additionally, the γ1-network, which is involved in phonetic feature binding, lacked engagement from posterior sensory hubs, forcing this critical process into a slow and effortful motor loop. The γ2-network exhibited unusual activation of right-hemisphere posterior areas during word processing, while it employed a simpler, less mature routing strategy for pseudoword listening, which further diminished global communication. Conclusions: This functionality highlights the core phonological and temporal processing deficits characteristic of dyslexia.