Alzheimer & Parkinson
Regulatory networks of KRAB zinc finger genes and transposable elements changed during human brain evolution and disease
Evidence indicates that transposable elements (TEs) can contribute to the evolution of new traits, with some TEs acting as deleterious elements while others are repurposed for beneficial roles in evolution. In mammals, some KRAB-ZNF proteins can serve as a key defense mechanism to repress TEs, offering genomic protection. Notably, the family of KRAB-ZNF genes evolves rapidly and exhibits diverse expression patterns in primate brains, where some TEs, including autonomous LINE-1 and non-autonomous...
Inhibition of Hippo Signaling Through Ablation of Lats1 and Lats2 Protects Against Cognitive Decline in 5xFAD Mice via Increasing Neuronal Resilience Against Ferroptosis
The Hippo signaling pathway is a key regulator of cell growth and cell survival, and hyperactivation of the Hippo pathway has been implicated in neurodegenerative diseases such as Huntington's disease. However, the role of Hippo signaling in Alzheimer's disease (AD) remains unclear. We observed that hyperactivation of Hippo signaling occurred in the AD model 5xFAD mice. To determine how inhibition of Hippo signaling might affect disease pathogenesis, we generated 5xFAD mice with conditional...
Hybridoma-inspired strategy crafts tailored multifunctional exosomes for precision therapy
Engineering functional exosomes represents a cutting-edge approach in biomedicine, holding the promise to transform targeted therapy. However, challenges such as achieving consistent modification and scalability have limited their wider adoption. Herein, we introduce a universal and effective strategy for engineering multifunctional exosomes through cell fusion. The hybrid-cell-derived exosomes could combine the functional properties of both parental cells and be readily produced by passaging....
A role for lithium in Alzheimer disease
No abstract
Microglia-to-neuron signaling links <em>APOE4</em> and inflammation to enhanced neuronal lipid metabolism and network activity
Microglia regulate neuronal circuit plasticity. Disrupting their homeostatic function has detrimental effects on neuronal circuit health. Neuroinflammation contributes to the onset and progression of neurodegenerative diseases, including Alzheimer's disease (AD), with several microglial activation genes linked to increased risk for these conditions. Inflammatory microglia alter neuronal excitability, inducing metabolic strain. Interestingly, expression of APOE4, the strongest genetic risk factor...
AlzFormer: Video-based space-time attention model for early diagnosis of Alzheimer's disease
Early and accurate Alzheimer's disease (AD) diagnosis is critical for effective intervention, but it is still challenging due to neurodegeneration's slow and complex progression. Recent studies in brain imaging analysis have highlighted the crucial roles of deep learning techniques in computer-assisted interventions for diagnosing brain diseases. In this study, we propose AlzFormer, a novel deep learning framework based on a space-time attention mechanism, for multiclass classification of AD,...
Cognitive prediction using regional connectivities and network biomarkers in Alzheimer's disease
Achieving a deep understanding of brain mechanisms requires multi-scale perspectives to capture the architecture of complex networks. In this study, we focused on patients with cognitive impairment and constructed individual brain networks from neuroimaging data. We introduced a Significant Edges Selection (SES) method, which effectively extracts the most informative connections while suppressing noise. Using these refined features, we computed network characteristics and applied machine...
Hemispheric asymmetry of tau pathology is related to asymmetric amyloid deposition in Alzheimer's Disease
The distribution of tau pathology in Alzheimer's disease (AD) shows remarkable inter-individual heterogeneity, including hemispheric asymmetry. However, the factors driving this asymmetry remain poorly understood. Here we explore whether tau asymmetry is linked to i) reduced inter-hemispheric brain connectivity (potentially restricting tau spread), or ii) asymmetry in amyloid-beta (Aβ) distribution (indicating greater hemisphere-specific vulnerability to AD pathology). We include 452...
Gut microbial production of imidazole propionate drives Parkinson's pathologies
Parkinson's disease (PD) is characterized by the selective degeneration of midbrain dopaminergic neurons and aggregation of α-synuclein. Emerging evidence implicates the gut microbiome in PD, with microbial metabolites proposed as potential pathological mediators. However, the specific microbes and metabolites involved, and whether gut-derived metabolites can reach the brain to directly induce neurodegeneration, remain unclear. Here we show that elevated levels of Streptococcus mutans (S....
A blood-based DNA damage signature in patients with Parkinson's disease is associated with disease progression
Aging is the main risk factor for Parkinson's disease (PD), yet our understanding of how age-related mechanisms contribute to PD pathophysiology remains limited. We conducted a longitudinal analysis of blood samples from the Parkinson's Progression Markers Initiative cohort to investigate DNA damage in PD. Patients with PD exhibited disrupted DNA repair pathways and biased suppression of longer transcripts, indicating age-related, transcription-stalling DNA damage. Notably, at the intake visit,...
Regulation of PPAR-γ coactivator-1α and its implication in mitochondrial function and neurodegenerative diseases
Peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC)-1α, interacts with numerous transcription factors implicated in a wide spectrum of biological responses. It has been identified as a key player in the transcriptional regulation of many mitochondrial components. The activity of PGC1-α is regulated at multiple levels, such as gene expression, transcriptional, post-transcriptional, and post-translational modification. The purpose of this review is to highlight the data...
Hydrogen sulfide in the brain as a silent neuroprotector in Alzheimer's disease
Hydrogen sulfide (H(2)S) is an endogenously produced gasotransmitter that has garnered growing attention for its critical roles in cellular signalling and brain function. It regulates NMDA receptors during long-term potentiation, a fundamental mechanism underlying memory consolidation and influences neurotransmission and essential neurophysiological functions. H(2)S is synthesized by three enzymes: cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS) and 3-mercaptopyruvate...
Advancing nanotheranostics for neuro-immunological disorders: current status and future prospects
Neuroimmunological disorders involve complex interactions between the nervous and immune systems, leading to various severe neurological conditions such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. These disorders are characterized by immune-mediated damage or inflammation within nervous tissue, resulting in cognitive deficits, movement issues, sensory impairments, and other neurological problems. They can affect people of all ages, but incidence increases significantly...
Artemisinin alleviates Parkinson's disease by targeting Adcy5-Gch1 axis to trigger a cascade generation of BH4 and dopamine in rats
CONCLUSIONS: Artemisinin mediates neuroprotection against Parkinson's disease via regulation of Adcy5-Gch1-BH4 axis in rats. These findings present a beneficial potential for future application of artemisinin on Parkinson's disease treatment.
Emerging roles for innate and adaptive immunity in tauopathies
Tauopathies encompass a large majority of dementia diagnoses and are characterized by toxic neuronal or glial inclusions of the microtubule-associated protein tau. Tau has a high propensity to induce prion-like spreading throughout the brain via a variety of mechanisms, making tauopathy a rapid and lethal form of neurodegeneration that currently lacks an effective therapy or cure. Tau aggregation and neuronal loss associated with this pathology are accompanied by robust neuroinflammation. Innate...
APOE4 Exacerbates Alzheimer-Like Pathologies and Cognitive Deficits Induced by Blood-Derived Abeta in a Mouse Model
Apolipoprotein E4 (APOE4) is a significant risk for both familial Alzheimer's disease (AD) and sporadic AD with elusive mechanisms. Previous studies mainly focused on the role of APOE4 in familial AD, with less attention to sporadic AD. Our previous study demonstrated that blood cell-derived amyloid-β (Aβ) can enter the brain and induce AD-like pathologies, providing a novel animal model to study sporadic AD to a certain extent. The impacts of APOE4 on Alzheimer-like pathologies and cognitive...
Innate immune sensing of Z-nucleic acids by ZBP1-RIPK1 axis drives neuroinflammation in Alzheimer's disease
Neuroinflammation drives Alzheimer's disease (AD) pathogenesis. Z-DNA, a non-canonical left-handed DNA structure, activates innate immune signaling through Z-DNA-binding protein 1 (ZBP1). However, the functional significance of ZBP1-mediated Z-DNA detection in AD remains undefined. Here, we found that ZBP1 is amplified in AD microglia, driving innate immune responses and neuroinflammation through sensing Z-form mitochondrial DNA (mtDNA). We show that oxidized mtDNA, generated by amyloid-β...
Tailoring the biomarkers of Alzheimer's disease using a gut microbiome-centric approach: Preclinical, clinical, and regulatory perspectives
Alzheimer's disease (AD), a progressive neurodegenerative disorder, poses significant therapeutic challenges due to its complex etiology and limited treatment options. Traditional pharmacotherapies targeting amyloid-β (Aβ) and cholinergic pathways offer modest benefits and are often associated with adverse effects. Emerging evidence implicates gut dysbiosis and the gut-brain axis in the pathogenesis and progression of AD. This review explores the multifactorial pathophysiology of AD and...
From adaptive deep brain stimulation to adaptive circuit targeting
Deep brain stimulation (DBS) substantially improves motor symptoms and quality of life in people with movement disorders such as Parkinson disease and dystonia, and it is also being explored as a treatment option for other brain disorders, including treatment-resistant obsessive-compulsive disorder, Alzheimer disease and depression. Two major developments are currently driving progress in DBS research: first, the framework of adaptive DBS, which senses brain activity to infer the momentary state...
Biomarker-related phospho-tau217 appears in synapses around Abeta plaques prior to tau tangle in cerebral cortex of preclinical Alzheimer's disease
Phospho-tau protein p-tau181 is a cerebrospinal fluid biomarker for Alzheimer's disease (AD), while p-tau217 is the most sensitive plasma biomarker for cerebral amyloid β (Aβ) load prior to tau pathology in preclinical AD. Diagnostic and prognostic use of these p-tau biomarkers requires neuropathological interpretation. Here, we analyzed the cellular localization of biomarker p-tau species in postmortem human brains harboring different extents of Aβ plaque and tau pathology. Signals for p-tau217...
Alzheimer and Parkinson: Latest results from PubMed
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