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Decline in mitochondrial quality is a prominent pathological feature of Alzheimer's disease (AD), manifested by impaired energy metabolism, disrupted mitochondrial biogenesis, abnormal mitochondrial dynamics, and defective mitophagy. Increasing evidence indicates that mitochondrial dysfunction contributes to the exacerbation of amyloid-β (Aβ) deposition and tau protein hyperphosphorylation, thereby accelerating AD pathogenesis. Of particular interest, physical exercise has been shown to effectively enhance mitochondrial quality and help prevent or slow the progression of AD, largely through the activation of key signaling pathways such as adenosine monophosphate-activated protein kinase (AMPK) and sirtuin 1 (SIRT1). However, regular physical activity may not be feasible for individuals in the prodromal or clinical stages of AD. In this context, exercise mimetics-compounds that pharmacologically simulate the molecular effects of exercise-have emerged as a promising alternative intervention. This review analyzes the mechanistic roles of exercise mimetics in improving mitochondrial quality under AD conditions, with a focus on their regulation of mitochondrial homeostasis via key signaling pathways. It further aims to provide theoretical insight for the development of mitochondria-targeted exercise mimetics and offer a potential strategy for addressing the growing global burden of AD. Show less

The number of people living with Alzheimer's disease (AD) is increasing worldwide as populations age. A hallmark of AD is the accumulation of amyloid-β (Aβ) in the brain, and pathways regulating amyloid-β precursor protein (AβPP) processing are of major interest for disease-modifying and preventive strategies such as exercise. Regular exercise is associated with a reduced risk of AD, potentially through limiting Aβ accumulation, yet the underlying cellular mechanisms remain unclear. Acute bouts of exercise induce the release of circulating signalling molecules that may influence AβPP metabolism. To investigate the effects of exercise on AβPP processing, human induced pluripotent stem cell (iPSC)-derived neurons and astrocytes were treated with serum collected before and immediately after high-intensity exercise. Both healthy control and familial AD (PSEN1 A246E) neurons and astrocytes were independently exposed to 10 % pre- or post-exercise serum for 30 min, after which markers of AβPP processing were quantified. Post-exercise serum contained increased amounts of Lacate, BDNF, IL-6, sAβPPα, and Aβ₁-₄₂, and reduced neprilysin activity (p < 0.05). Treatment with post-exercise serum acutely elevated ADAM10 activity in neurons, which was replicated by spiking lactate in pre-exercise serum. sAβPPα was also increased in PSEN1 neurons following post exercise serum treatment with increased Aβ₁-₄₂ secretion in both PSEN1 neurons and astrocytes (p < 0.05). These findings demonstrate that human post-exercise serum can modulate AβPP processing in iPSC-derived neural cells. This supports the concept that circulating exercise-induced factors can influence neuronal pathways relevant to AD pathology. Show less

Alzheimer's disease (AD) is a common neurodegenerative disorder wherein reactive oxygen species (ROS) and Amyloid-β-protein (Aβ) play critical roles. Inspired by traditional Chinese charcoal drug and the anti-inflammatory properties of some carbon dots, we developed Radix Isatidis derived carbon dots (RI-CDs) via a hydrothermal method. The RI-CDs can cross the blood-brain barrier (BBB) and were thus evaluated for AD therapy. In vitro, RI-CDs scavenged ROS, inhibited Aβ Show less

Alzheimer's disease is a common neurodegenerative disease characterized by progressive memory loss, cognitive decline, and behavioral changes. Blood-based biomarkers have recently gained significant attention due to their accessibility and cost-effectiveness. This review highlights the latest progress in multiple key areas of bloodbased biomarkers for Alzheimer's disease. For early diagnosis, blood-based biomarkers such as amyloid-β and phosphorylated tau can identify Alzheimer's disease even before clinical symptoms emerge. Dynamic changes in blood-based biomarkers, including p-tau217 and neurofilament light chain, reflect disease progression and correlate with cognitive decline, enabling continuous monitoring of Alzheimer's disease progression. Additionally, bloodbased biomarkers such as p-tau181 and glial fibrillary acidic protein aid in differential diagnosis by distinguishing Alzheimer's disease from other dementias such as frontotemporal dementia. Blood-based biomarkers related to nerve repair have opened up new avenues for tracking nerve regeneration and therapeutic response, especially brain-derived neurotrophic factor. Furthermore, advanced detection technologies such as single-molecule array and immunoprecipitation-mass spectrometry have significantly improved the sensitivity and specificity of bloodbased biomarkers, facilitating their clinical translation. In summary, blood-based biomarkers hold strong potential to improve early diagnosis, monitor progression, differential diagnosis, and evaluate therapies in Alzheimer's disease. This review provides a comprehensive and updated evaluation of the translational potential of bloodbased biomarkers, emphasizing their practical utility in clinical settings and offering insights into future directions for large-scale application. This review emphasizes the need to prioritize the allocation of scientific resources, expedite the transition of blood-based biomarkers to clinical implementation, and ultimately achieve precise treatment of Alzheimer's disease using these biomarkers. Show less

The strong relationship between Alzheimer's Disease (AD) and diabetes mellitus (DM) is described by the term "type 3 diabetes". Canagliflozin (CAN), a sodium-glucose co-transporter 2 inhibitor (SGLT2i), is an antidiabetic agent under investigation as a potential new treatment for AD due to its acetylcholinesterase (AChE) inhibitory properties. We aimed to examine the effect of CAN on the efficacy of the anti-acetylcholinesterase, rivastigmine (RIV), against aluminum chloride (AlCl Show less