Distribution and inter-regional relationship of amyloid-beta plaque deposition in a 5xFAD mouse model of Alzheimer’s disease

Alzheimer’s disease (AD) is the most common form of dementia. Although previous studies have selectively investigated the localization of amyloid-beta (Aβ) deposition in certain brain regions, a comprehensive characterization of the rostro-caudal distribution of Aβ plaques in the brain and their inter-regional correlation remain unexplored. Our results demonstrated remarkable working and spatial memory deficits in 9-month-old 5xFAD mice compared to wildtype mice. High Aβ plaque load was detected in the somatosensory cortex, piriform cortex, thalamus, and dorsal/ventral hippocampus; moderate levels of Aβ plaques were observed in the motor cortex, orbital cortex, visual cortex, and retrosplenial dysgranular cortex; and low levels of Aβ plaques were located in the amygdala, and the cerebellum; but no Aβ plaques were found in the hypothalamus, raphe nuclei, vestibular nucleus, and cuneate nucleus. Interestingly, the deposition of Aβ plaques was positively associated with brain inter-regions including the prefrontal cortex, somatosensory cortex, medial amygdala, thalamus, and the hippocampus. In conclusion, this study provides a comprehensive morphological profile of Aβ deposition in the brain and its inter-regional correlation. This suggests an association between Aβ plaque deposition and specific brain regions in AD pathogenesis

Mimicking multiple sclerosis - Ghost tumor that comes and goes in different parts of the brain without any treatment

Lesions that spontaneously come and go in central nervous system without any treatment at different time points and at different locations (CNS) usually lead ones to think of the possibilities of multiple sclerosis. However, sometimes there are exceptions. Surgical biopsy remains an important tool for definitive diagnosis in difficult cases. We report a case of intracranial diffuse large B cell lymphoma that spontaneously disappeared without any treatment and then reappeared at different time points and different locations

Discovery of Therapeutics Targeting Oxidative Stress in Autosomal Recessive Cerebellar Ataxia: A Systematic Review

Autosomal recessive cerebellar ataxias (ARCAs) are a heterogeneous group of rare neurodegenerative inherited disorders. The resulting motor incoordination and progressive functional disabilities lead to reduced lifespan. There is currently no cure for ARCAs, likely attributed to the lack of understanding of the multifaceted roles of antioxidant defense and the underlying mechanisms. This systematic review aims to evaluate the extant literature on the current developments of therapeutic strategies that target oxidative stress for the management of ARCAs. We searched PubMed, Web of Science, and Science Direct Scopus for relevant peer-reviewed articles published from 1 January 2016 onwards. A total of 28 preclinical studies fulfilled the eligibility criteria for inclusion in this systematic review. We first evaluated the altered cellular processes, abnormal signaling cascades, and disrupted protein quality control underlying the pathogenesis of ARCA. We then examined the current potential therapeutic strategies for ARCAs, including aromatic, organic and pharmacological compounds, gene therapy, natural products, and nanotechnology, as well as their associated antioxidant pathways and modes of action. We then discussed their potential as antioxidant therapeutics for ARCAs, with the long-term view toward their possible translation to clinical practice. In conclusion, our current understanding is that these antioxidant therapies show promise in improving or halting the progression of ARCAs. Tailoring the therapies to specific disease stages could greatly facilitate the management of ARCAs

Discovery of Therapeutics Targeting Oxidative Stress in Autosomal Recessive Cerebellar Ataxia: A Systematic Review

Autosomal recessive cerebellar ataxias (ARCAs) are a heterogeneous group of rare neurodegenerative inherited disorders. The resulting motor incoordination and progressive functional disabilities lead to reduced lifespan. There is currently no cure for ARCAs, likely attributed to the lack of understanding of the multifaceted roles of antioxidant defense and the underlying mechanisms. This systematic review aims to evaluate the extant literature on the current developments of therapeutic strategies that target oxidative stress for the management of ARCAs. We searched PubMed, Web of Science, and Science Direct Scopus for relevant peer-reviewed articles published from 1 January 2016 onwards. A total of 28 preclinical studies fulfilled the eligibility criteria for inclusion in this systematic review. We first evaluated the altered cellular processes, abnormal signaling cascades, and disrupted protein quality control underlying the pathogenesis of ARCA. We then examined the current potential therapeutic strategies for ARCAs, including aromatic, organic and pharmacological compounds, gene therapy, natural products, and nanotechnology, as well as their associated antioxidant pathways and modes of action. We then discussed their potential as antioxidant therapeutics for ARCAs, with the long-term view toward their possible translation to clinical practice. In conclusion, our current understanding is that these antioxidant therapies show promise in improving or halting the progression of ARCAs. Tailoring the therapies to specific disease stages could greatly facilitate the management of ARCAs

Sex Differences between Neuronal Loss and the Early Onset of Amyloid Deposits and Behavioral Consequences in 5xFAD Transgenic Mouse as a Model for Alzheimer's Disease

A promising direction in the research on Alzheimer's Disease (AD) is the identification of biomarkers that better inform the disease progression of AD. However, the performance of amyloid-based biomarkers in predicting cognitive performance has been shown to be suboptimal. We hypothesise that neuronal loss could better inform cognitive impairment. We have utilised the 5xFAD transgenic mouse model that displays AD pathology at an early phase, already fully manifested after 6 months. We have evaluated the relationships between cognitive impairment, amyloid deposition, and neuronal loss in the hippocampus in both male and female mice. We observed the onset of disease characterized by the emergence of cognitive impairment in 6-month-old 5xFAD mice coinciding with the emergence of neuronal loss in the subiculum, but not amyloid pathology. We also showed that female mice exhibited significantly increased amyloid deposition in the hippocampus and entorhinal cortex, highlighting sex-related differences in the amyloid pathology of this model. Therefore, parameters based on neuronal loss might more accurately reflect disease onset and progression compared to amyloid-based biomarkers in AD patients. Moreover, sex-related differences should be considered in studies involving 5xFAD mouse models.</p