Despite the growing interest in cell- and exosome-based therapies for neurological diseases including Alzheimer's disease (AD), there is still a gap in the investigation of more effective treatments i Show more
Despite the growing interest in cell- and exosome-based therapies for neurological diseases including Alzheimer's disease (AD), there is still a gap in the investigation of more effective treatments in terms of efficacy, safety, and durability of effect. This study aimed to compare the therapeutic potential of astrocyte cells and their derived exosomes (AS-Exos) in restoring cognitive function in a mouse model of AD. AD model was induced by bilateral electrical lesioning of the nucleus basalis of Meynert (NBM). Astrocytes were isolated from neonatal rat brains, and AS-Exos were harvested from astrocyte-conditioned media using an AnaCell extraction kit. Seven days after lesion induction, astrocytes and AS-Exos were stereotaxically injected into the NBM. Four weeks later, behavioral assessments (passive avoidance and locomotor activity), electrophysiological recordings (EEG), and biochemical measurements of hippocampal brain-derived neurotrophic factor (BDNF) and acetylcholine (ACh) levels were performed. AS-Exos were confirmed as cup-shaped vesicles (30-150 nm) expressing the exosomal surface markers CD9, CD63, and CD81. NBM lesions significantly reduced step-through latency (STL), hippocampal BDNF and ACh levels, and disrupted EEG oscillatory patterns. Treatment with AS-Exos markedly improved STL and produced greater increases in hippocampal BDNF and ACh levels compared with AD and AD+saline groups. EEG analysis also revealed enhanced beta, alpha, and gamma power, with the most robust normalization observed in the AS-Exos group. AS-Exos demonstrated superior biochemical and electrophysiological benefits compared with astrocyte transplantation and provided equal or greater improvement in behavioral outcomes. These findings highlight AS-Exos as a promising cell-free therapeutic strategy for alleviating cognitive deficits associated with AD. Show less
The Gold Coast criteria permit diagnosis of amyotrophic lateral sclerosis (ALS) even without upper motor neuron (UMN) signs. However, whether ALS patients with UMN signs (ALSwUMN) and those without (A Show more
The Gold Coast criteria permit diagnosis of amyotrophic lateral sclerosis (ALS) even without upper motor neuron (UMN) signs. However, whether ALS patients with UMN signs (ALSwUMN) and those without (ALSwoUMN) share similar characteristics and prognoses remains unclear. This study compared clinical features, disease progression, electrophysiological findings, biomarker profiles, imaging parameters, and survival between these groups. ALS patients diagnosed according to the Gold Coast criteria were classified into ALSwUMN (n = 51) and ALSwoUMN (n = 20) groups. We evaluated clinical data, motor evoked potentials (MEP), and serum biomarkers, including cardiac Troponin T, neurofilament light chain, glial fibrillary acidic protein, and brain-derived neurotrophic factor. Imaging parameters, including cortical thickness and white matter volume, were also evaluated. Survival was analyzed using the Kaplan-Meier method. The groups showed broadly similar clinical features, disease progression, and biomarker profiles. Abnormal MEPs were more frequent in ALSwUMN (94.0%) than in ALSwoUMN (63.2%, p = 0.017). Both groups demonstrated cortical thinning in the precentral and entorhinal regions compared to healthy controls. ALSwUMN exhibited thinning in the lateral orbitofrontal, insular, and temporal pole regions, while ALSwoUMN showed thinning in the pars opercularis. White matter volume was reduced in both groups in the thalamus, cerebellum, and amygdala, with additional brainstem atrophy in ALSwUMN. No significant survival difference was observed. Despite minor distinctions in electrophysiological and imaging findings, ALSwoUMN had overall comparable clinical profiles and outcomes to ALSwUMN. These findings support recognizing ALSwoUMN within the ALS spectrum under the Gold Coast criteria. Show less