Changes in β-amyloid (Aβ) and hyperphosphorylated tau (T) in brain and cerebrospinal fluid (CSF) precede Alzheimer's disease (AD) symptoms, making the CSF proteome a potential avenue to understand disease pathophysiology and facilitate reliable diagnostics and therapies. Using the AT framework and a three-stage study design (discovery, replication, and meta-analysis), we identified 2,173 analytes (2,029 unique proteins) dysregulated in AD. Of these, 865 (43%) were previously reported, and 1,164 (57%) are novel.

The article provides a comprehensive review of the role of semaphorin 3A (Sema3A) in the pathogenesis and progression of Alzheimer's disease and other aging-related diseases. It discusses the expression patterns and mechanisms of action of Sema3A in various age-related disorders, including its involvement in oxidative stress, inflammatory responses, apoptosis, and synaptic plasticity.

The article discusses the role of gut dysbiosis, bacterial amyloids, and metabolic diseases in the development and progression of Alzheimer's disease (AD). It highlights the bidirectional relationship between the gut microbiome, inflammation, and metabolic disorders, and how these interconnected pathways contribute to neurodegeneration. The review explores potential therapeutic strategies targeting the gut-brain-metabolic axis to mitigate AD progression.

This systematic review examined the relationship between cognition and motor speech production in healthy older adults and those with mild cognitive impairment, analyzing 22 studies with 747 participants. Findings suggest that cognitive functions, particularly attention and executive abilities, are linked to motor speech performance, though evidence quality varies and gaps remain.

Microglia are immune cells of the central nervous system, playing a vital role in brain development, homeostasis, and disease. When these cells become dysfunctional, they can contribute to various psychiatric disorders and neurodegenerative diseases. To enhance our understanding of microglial function, researchers are increasingly employing human cell-based models. This approach significantly improves our investigations into these complex conditions and aids in ongoing drug development efforts.

The article describes the discovery and development of compound 8e, a selective and reversible butyrylcholinesterase (BuChE) inhibitor, as a potential therapeutic agent for treating Alzheimer's disease (AD). Compound 8e exhibited favorable blood-brain barrier permeability, good drug-likeness properties, and pronounced neuroprotective efficacy in various AD models, including zebrafish, scopolamine-induced mice, and APP/PS1 transgenic mice.

This study demonstrated that physical exercise pretreatment improves recognition memory and enhances structural synaptic plasticity in the hippocampus of Alzheimer’s disease (AD) rats, primarily through the activation of hippocampal TREM2. Blocking TREM2 diminished these neuroprotective effects, indicating that exercise mitigates synaptic injury and cognitive decline in AD via a TREM2-dependent mechanism.

This study examined perceptions and awareness of brain health among Cuban youth through an online survey of 1,049 participants using the Global Brain Health Survey. Results showed that participants viewed the social environment as the most influential factor on brain health and were generally aware of conditions like Alzheimer’s and depression, but had limited understanding of the cognitive effects of chronic diseases such as hypertension and diabetes, underscoring the need for targeted public health education and awareness campaigns.

This study demonstrates that aerobic exercise, specifically swimming training, improves learning and memory in Alzheimer's disease model mice by enhancing glymphatic system function and promoting AQP4 polarization, which facilitates clearance of β-amyloid in the hippocampus. These findings suggest that exercise-induced upregulation of Lama1 and Dp71 supports glymphatic clearance mechanisms, thereby reducing Aβ deposition and cognitive impairment.

The article discusses the role of microglial activation in Alzheimer's disease (AD), highlighting its impact on neuroinflammation and cognitive dysfunction. It explores the molecular mechanisms underlying microglial activation, potential therapeutic targets, and updates on clinical trials for drugs aimed at mitigating neuroinflammation and cognitive decline in AD.