Axonal degeneration in the anterior insular cortex is associated with Alzheimer ’s co-pathology in Parkinson’s disease and dementia with Lewy bodies
ConclusionsOur results highlight the selective vulnerability of the anterior insular sub-regions to various converging pathologies, leading to impaired axonal integrity in PD, PDD and DLB, disrupting their functional properties and potentially contributing to cognitive, emotional, and autonomic deficits. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - December 7, 2022 Category: Neurology Source Type: research
Deep brain stimulation of the nucleus basalis of Meynert modulates hippocampal –frontoparietal networks in patients with advanced Alzheimer’s disease
ConclusionThe results indicated that NBM-DBS improves short-term cognitive performance in patients with advanced AD, which may be related to the modulation of multi-network connectivity patterns, and the hippocampus plays an important role within these networks.Trial registrationChiCTR, ChiCTR1900022324. Registered 5 April 2019 —Prospective registration.https://www.chictr.org.cn/showproj.aspx?proj=37712 (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - December 5, 2022 Category: Neurology Source Type: research
Dual role of brain-derived extracellular vesicles in dementia-related neurodegenerative disorders: cargo of disease spreading signals and diagnostic-therapeutic molecules
AbstractNeurodegenerative disorders are one of the most common causes of disability and represent 6.3% of the global burden of disease. Among them, Alzheimer ’s, Parkinson’s, and Huntington’s diseases cause cognitive decline, representing the most disabling symptom on both personal and social levels. The molecular mechanisms underlying the onset and progression of dementia are still poorly understood, and include secretory factors potentially affec ting differentiated neurons, glial cells and neural stem cell niche. In the last decade, much attention has been devoted to exosomes as novel carriers of information excha...
Source: Translational Neurodegeneration - November 27, 2022 Category: Neurology Source Type: research
Gut microbiome, cognitive function and brain structure: a multi-omics integration analysis
ConclusionsOur findings reveal that specific gut microbial features are closely associated with cognitive impairment and decreased hippocampal volume, which may play an important role in dementia development. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - November 14, 2022 Category: Neurology Source Type: research
Deciphering lipid dysregulation in ALS: from mechanisms to translational medicine
AbstractLipids, defined by low solubility in water and high solubility in nonpolar solvents, can be classified into fatty acids, glycerolipids, glycerophospholipids, sphingolipids, and sterols. Lipids not only regulate integrity and fluidity of biological membranes, but also serve as energy storage and bioactive molecules for signaling. Causal mutations inSPTLC1 (serine palmitoyltransferase long chain subunit 1) gene within the lipogenic pathway have been identified in amyotrophic lateral sclerosis (ALS), a paralytic and fatal motor neuron disease. Furthermore, lipid dysmetabolism within the central nervous system and circ...
Source: Translational Neurodegeneration - November 7, 2022 Category: Neurology Source Type: research
Myelin repair in Alzheimer ’s disease: a review of biological pathways and potential therapeutics
AbstractThis literature review investigates the significant overlap between myelin-repair signaling pathways and pathways known to contribute to hallmark pathologies of Alzheimer ’s disease (AD). We discuss previously investigated therapeutic targets of amyloid, tau, and ApoE, as well as other potential therapeutic targets that have been empirically shown to contribute to both remyelination and progression of AD. Current evidence shows that there are multiple AD-relevant p athways which overlap significantly with remyelination and myelin repair through the encouragement of oligodendrocyte proliferation, maturation, and m...
Source: Translational Neurodegeneration - October 26, 2022 Category: Neurology Source Type: research
Association of variants in the KIF1A gene with amyotrophic lateral sclerosis
ConclusionsOur study highlighted the importance of KIF1A motor-mediated transport in the pathogenesis of ALS, indicatingKIF1A as an important player in the oligogenic scenario of ALS. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - October 26, 2022 Category: Neurology Source Type: research
APOE ε4-dependent effects on the early amyloid pathology in induced neurons of patients with Alzheimer’s disease
ConclusionsOur findings suggest that the presence ofAPOEε4 at the early Aβ-seeding stage in patient iNs is critical for aggravation of sporadic AD pathology. These results provide insights into the importance ofAPOEε4 expression for the progression and pathogenesis of sporadic AD. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - October 25, 2022 Category: Neurology Source Type: research
Intestine-derived α-synuclein initiates and aggravates pathogenesis of Parkinson’s disease in Drosophila
ConclusionsThe intestinal expression of α-syn recapitulates many phenotypic and pathologic features of PD, and induces dysbiosis that aggravates the pathology through the DUOX–ROS–JNK pathway inDrosophila. Our findings provide new insights into the role of intestinal α-syn in PD pathophysiology. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - October 17, 2022 Category: Neurology Source Type: research
Why do ‘OFF’ periods still occur during continuous drug delivery in Parkinson’s disease?
AbstractContinuous drug delivery (CDD) is used in moderately advanced and late-stage Parkinson ’s disease (PD) to control motor and non-motor fluctuations (‘OFF’ periods). Transdermal rotigotine is indicated for early fluctuations, while subcutaneous apomorphine infusion and levodopa-carbidopa intestinal gel are utilised in advanced PD. All three strategies are considered examples of co ntinuous dopaminergic stimulation achieved through CDD. A central premise of the CDD is to achieve stable control of the parkinsonian motor and non-motor states and avoid emergence of ‘OFF’ periods. However, data suggest that desp...
Source: Translational Neurodegeneration - October 13, 2022 Category: Neurology Source Type: research
CRISPR/dCas9-Dnmt3a-mediated targeted DNA methylation of APP rescues brain pathology in a mouse model of Alzheimer ’s disease
ConclusionsThese results suggest that the targeted methylation ofAPPvia dCas9-Dnmt3a treatment can be a potential therapeutic strategy for AD. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - September 15, 2022 Category: Neurology Source Type: research
A review of brain imaging biomarker genomics in Alzheimer ’s disease: implementation and perspectives
AbstractAlzheimer ’s disease (AD) is a progressive neurodegenerative disease with phenotypic changes closely associated with both genetic variants and imaging pathology. Brain imaging biomarker genomics has been developed in recent years to reveal potential AD pathological mechanisms and provide early diagnoses. Th is technique integrates multimodal imaging phenotypes with genetic data in a noninvasive and high-throughput manner. In this review, we summarize the basic analytical framework of brain imaging biomarker genomics and elucidate two main implementation scenarios of this technique in AD studies: (1) ex ploring no...
Source: Translational Neurodegeneration - September 15, 2022 Category: Neurology Source Type: research
The COVID-19 pandemic and Alzheimer ’s disease: mutual risks and mechanisms
AbstractCoronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a life-threatening disease, especially in elderly individuals and those with comorbidities. The predominant clinical manifestation of COVID-19 is respiratory dysfunction, while neurological presentations are increasingly being recognized. SARS-CoV-2 invades host cells primarily via attachment of the spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor expressed on cell membranes. Patients with Alzheimer’s disease (AD) are more susceptible to SARS-CoV-2 infection and prone to s...
Source: Translational Neurodegeneration - September 11, 2022 Category: Neurology Source Type: research
The emerging role of furin in neurodegenerative and neuropsychiatric diseases
AbstractFurin is an important mammalian proprotein convertase that catalyzes the proteolytic maturation of a variety of prohormones and proproteins in the secretory pathway. In the brain, the substrates of furin include the proproteins of growth factors, receptors and enzymes. Emerging evidence, such as reducedFURIN mRNA expression in the brains of Alzheimer ’s disease patients or schizophrenia patients, has implicated a crucial role of furin in the pathophysiology of neurodegenerative and neuropsychiatric diseases. Currently, compared to cancer and infectious diseases, the aberrant expression of furin and its pharmaceut...
Source: Translational Neurodegeneration - August 23, 2022 Category: Neurology Source Type: research
Correction: Olfactory swab sampling optimization for α-synuclein aggregate detection in patients with Parkinson’s disease
(Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - August 12, 2022 Category: Neurology Source Type: research
