Neurodegenerative Diseases最新文献

In the article “Characteristics of Neuromuscular Ultrasound in Patients with Amyotrophic Lateral Sclerosis” [Neurodegener Dis. 2025; https://doi.org/10.1159/000546425] by Wu et al., the wrong copyright license was displayed. It has been corrected to a CC-BY 4.0 license.The original online article has been updated to reflect this.

Background: Osteoporosis and Alzheimer's disease (AD) are age-related disorders with shared risk factors such as aging, oxidative stress, and neuroinflammation. Sclerostin, a glycoprotein secreted by osteocytes, inhibits Wnt/β-catenin signaling, leading to suppressed bone formation and increased resorption in osteoporosis. Recent findings reveal sclerostin is also expressed in the brain, where it may disrupt synaptic function and contribute to AD progression. Romosozumab, an anti-sclerostin monoclonal antibody approved for osteoporosis, is being explored for potential use in AD, though its ability to cross the blood-brain barrier remains a challenge.

Summary: This review highlights the emerging connection between osteoporosis and AD, focusing on sclerostin as a shared molecular mediator. Understanding this link may open new avenues for dual-purpose therapies targeting sclerostin, with the potential to benefit both bone and brain health. Further studies are needed to clarify the causal mechanisms and therapeutic implications.

Key messages: This review highlights sclerostin as a key molecular link between osteoporosis and AD, supporting the emerging concept of a bone-brain axis. Anti-sclerostin therapies like romosozumab may offer benefits beyond bone health, with potential in neurodegenerative disease treatment. Sclerostin may drive AD pathology by disrupting Wnt/β-catenin signaling and promoting β-amyloid and tau abnormalities.

Background: Alzheimer's disease (AD), the most common cause of dementia, affects twice as many women as men. Moreover, sex is increasingly recognised as an important factor for AD, influencing symptom presentation, progression, disease biology, and treatment responses. In parallel, AD biomarkers are becoming more accessible with the discovery of specific and accurate blood-based biomarkers and their incorporation in AD diagnostic frameworks. This narrative review aimed to summarise sex differences in the concentration and interpretation of biofluid biomarkers for AD.

Summary: Biological sex may influence both the concentration and interpretation of biofluid biomarkers for AD pathology such as amyloid-β aggregation, tau neurofibrillary tangles, neurodegeneration, or neuroinflammation. While some biofluid biomarkers display consistent sex differences in absolute levels, most biomarker levels have not been found to differ consistently by sex. Nonetheless, even biomarkers that do not differ in absolute levels display sex-specific associations with clinically relevant variables such as brain atrophy, cognitive impairment, and disease progression.

Key message: Sex may influence the interpretation of AD biomarkers depending on their context of use, and more research is required to develop sex-specific guidelines. Future research should aim to study sex differences and sex-specific associations with variables of interest, as well as the underlying factors driving sex differences in AD.

Introduction: Advancing age is associated with global brain atrophy. Cross-sectional studies have found sex differences in neuroanatomy; however, longitudinal studies assessing sex differences in neurodegeneration are currently scarce. The effects of age and sex on brain atrophy may not be uniform across the whole brain and may partially explain the sex differences observed in dementia. The current study aimed to examine sex differences in longitudinal atrophy patterns in gray and white matter regions in older adults.

Methods: The study sample included 1,480 individuals from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, a population-based cohort study, that underwent two magnetic resonance imaging scans within an average of 5 years between assessments. Individuals were also followed-up for incident dementia diagnosis. Linear regression models were used to assess sex differences between mean differences in gray and white matter regions, correcting for age, education, baseline intracranial volume, baseline regional volumes, hypertension, body mass index, and apolipoprotein (APOE) e4 allele status.

Results: Men showed increased longitudinal atrophy in the total gray matter, as well as in the parietal cortex, cingulate cortex, caudate nucleus, brainstem, left cerebellum, precentral gyrus, putamen, globus pallidus, and orbitofrontal cortex. Whereas women exhibited greater atrophy over time in total white matter, but not in specific regions. No moderation was found between sex differences in incident dementia regarding atrophy patterns.

Conclusions: While men show larger gray matter volumes cross-sectionally, their rates of atrophy over time are steeper compared to women. Sex differences in brain atrophy seem to be specifically detrimental in men in regions related to executive functioning, motor control, and emotion processing.

Background: The glymphatic system is a waste clearance system that facilitates the efficient removal of interstitial solutes, including neurotoxic substances such as β-amyloid, from the central nervous system. Numerous studies have highlighted its pivotal role in the pathophysiology of neurodegenerative diseases and cerebrospinal fluid (CSF) disorders. A comprehensive understanding and accurate evaluation of the glymphatic system are of significant clinical importance. Furthermore, emerging evidence suggests that modulating glymphatic activity holds therapeutic potential, including enhancing drug delivery across the brain.

Summary: This review consolidates current insights into the glymphatic system, addressing areas of consensus as well as ongoing controversies. The relationship between glymphatic dysfunction and CSF disorders is discussed, alongside advancements in evaluation methodologies. Additionally, therapeutic applications of glymphatic modulation are summarized, particularly its role in optimizing drug distribution within the brain.

Key messages: This review provides a comprehensive overview of the current knowledge on the glymphatic system and highlights imaging techniques used to assess human glymphatic function, including magnetic resonance imaging (MRI) with contrast agents, diffusion tensor imaging, and emerging techniques such as MRI with 17O-labeled water. Furthermore, the therapeutic implications of glymphatic modulation are discussed, and directions for future research are proposed.

Introduction: Many studies demonstrate positive associations between infections and Alzheimer disease (AD), suggesting that brain and/or systemic inflammation may impact AD pathogenesis. However, studies of meningitis and AD risk have been limited to animal models or small human cohorts in the USA. The objective of this study was to examine the relationship between incident AD and three different types of infections (meningitis, pneumonia, and urinary tract infections [UTIs]) using a population-based sample of US Medicare beneficiaries.

Methods: We created a case-control dataset by frequency matching 4:1 (control:case) by age group, sex, and month/year of the date of AD diagnosis or control selection date. We identified 52,628 newly diagnosed AD cases and 210,512 population-based controls ≥67 years of age using comprehensive Medicare claims data from 2016 to 2018. We classified infections using ICD-9-CM and ICD-10-CM diagnosis codes. We used logistic regression to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the association between AD and each infection separately. We lagged exposures up to 18 months and examined hospitalization or comorbid sepsis as a proxy for infection severity. Covariates included age, sex, race/ethnicity, and health care utilization.

Results: AD was positively associated with meningitis in individuals hospitalized without superimposed sepsis with a 6-month lag (OR = 2.713, 95% CI: 1.277-5.764), and UTIs without superimposed sepsis with an 18-month lag (OR = 1.231, 95% CI: 1.101-1.376), and with superimposed sepsis with an 18-month lag (OR = 1.388, 95% CI: 1.050-1.835). There was no association between AD and pneumonia in individuals hospitalized with or without superimposed sepsis. When examining infections that occurred in the outpatient setting, the association between AD and UTI remained positive yet attenuated at all time points, however, the association became inverse between AD and pneumonia.

Conclusion: More severe infections, particularly meningitis, may be associated with a higher risk of AD, due to either unmasking of prodromal AD or acceleration of AD pathogenesis in susceptible individuals.

Introduction: Neuromuscular ultrasound has been increasingly used in the detection and diagnosis of amyotrophic lateral sclerosis (ALS), commonly characterized by peripheral nerve atrophy, degeneration, and muscle fasciculations. The aim of this study was to assess the ultrasound characteristics of ALS patients.

Methods: A total of 67 consecutive patients with sporadic ALS and 19 with ALS mimics (63.16% peripheral neuropathy) were recruited. Ultrasound and electrophysiological examinations were performed; the peripheral nerve cross-sectional area (CSA) and fasciculation grades were compared between the groups, and correlations between ultrasound and electrophysiological data in ALS patients were determined.

Results: ALS patients had smaller proximal median and ulnar nerve CSAs than those of ALS mimics, who exhibited asymmetric changes. Fasciculation differences in the trapezius, triceps brachii, extensor digitorum communis, thenar, and first dorsal interosseous muscles were observed. In ALS patients, the CSA and fasciculation relative scores were correlated with electrophysiological indicators.

Conclusion: Ultrasound is a valuable tool for monitoring peripheral nerve CSA and muscle fasciculations, both of which correlate with electrophysiological indices, in ALS patients.

Background: Alzheimer's disease - an age-related neurodegenerative disorder leading to progressive cognitive impairment - is characterized by an intracerebral accumulation of soluble β-amyloid (Aβ) oligomers, followed by the appearance of abnormally ubiquitinylated neurofibrillary tangles - a process associated with a chronic inflammation. The systematic presence of ubiquitinylated inclusions reflects a decrease in the proteasome activity due to (and contributing to) the presence of Aβ oligomers - a central dysfunction in the etiology of the disease.

Summary: The involvement of the ubiquitin-proteasome system opens new therapeutic perspectives for both prevention and treatment. In particular, the potential for synergistic strategies combining diet-derived proteasome activators, immunoproteasome inhibitors, and modulators of Aβ peptide aggregation to prevent, delay or even reverse disease progression over time is currently arousing growing interest.

Key messages: From that perspective, and in light of the recent advances in the understanding of the key molecular and cellular mechanisms underlying Alzheimer's disease pathogenesis, the present review highlights the mechanisms of action and the preventive and therapeutic potential of some diet-derived bioactive compounds and other natural substances of interest. This article is a translated, updated, and expanded version of an article originally published in French in Médecine/Sciences, August/September 2023 (https://doi.org/10.1051/medsci/2023094).