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Alzheimer & Parkinson

Fatigue brain network functional connectivity in Parkinson's disease

3 months 1 week ago
Fatigue is a nonmotor symptom that negatively affects Parkinson's disease (PD) patients' quality of life. The study of fatigue is complex and the brain functional neural underpinnings of fatigue in PD are yet to be clarified. The aim of this study was to investigate the functional connectivity (FC) of the fatigue brain network in PD-related fatigue symptomatology. Forty-nine PD patients, divided into PD patients with fatigue (PD-f) and PD patients with no fatigue (PD-nf), and 33 healthy controls...
Oihana Zabala-Gómez

Astrocyte induction of disease-associated microglia is suppressed by acute exposure to fAD neurons in human iPSC triple cultures

3 months 1 week ago
Advancements in human induced pluripotent stem cell (hiPSC) technology have enabled co-culture models for disease modeling in physiologically relevant systems. However, co-culturing protocols face challenges in usability and consistency. Here, we introduce a robust, reproducible hiPSC-derived co-culture system integrating astrocytes, neurons, and microglia. This model leverages cryopreserved cells, enabling co-cultures within 20 days post-thaw. Comparing monocultures and tricultures, we...
Alexandra M Lish

Context-dependent modulations of subthalamo-cortical synchronization during rapid reversals of movement direction in Parkinson's disease

3 months 1 week ago
The role of beta band activity in cortico-basal ganglia interactions during motor control has been studied extensively in resting-state and for simple movements, such as button pressing. However, little is known about how beta oscillations change and interact in more complex situations involving rapid changes of movement in various contexts. To close this knowledge gap, we combined magnetoencephalography (MEG) and local field potential recordings from the subthalamic nucleus (STN) in Parkinson's...
Lucie Winkler

Intracellular accumulation of amyloid-ss is a marker of selective neuronal vulnerability in Alzheimer's disease

3 months 1 week ago
Defining how amyloid-β and pTau together lead to neurodegeneration is fundamental to understanding Alzheimer's disease (AD). We used imaging mass cytometry to identify neocortical neuronal subtypes lost with AD in post-mortem brain middle temporal gyri from non-diseased and AD donors. Here we showed that L5,6 RORB^(+)FOXP2^(+) and L3,5,6 GAD1^(+)FOXP2^(+) neurons, which accumulate amyloid-β intracellularly from early Braak stages, are selectively vulnerable to degeneration in AD, while L3...
Alessia Caramello

An AI-assisted fluorescence microscopic system for screening mitophagy inducers by simultaneous analysis of mitophagic intermediates

3 months 1 week ago
Mitophagy, the selective autophagic elimination of mitochondria, is essential for maintaining mitochondrial quality and cell homeostasis. Impairment of mitophagy flux, a process involving multiple sequential intermediates, is implicated in the onset of numerous neurodegenerative diseases. Screening mitophagy inducers, particularly understanding their impact on mitophagic intermediates, is crucial for neurodegenerative disease treatment. However, existing techniques do not allow simultaneous...
Yicheng Wang

Electrochemical sensor toolkit for simultaneous glutamate detection at edge of cleft and peri-soma

3 months 1 week ago
Simultaneously monitoring glutamate (Glu) dynamic at edge of synaptic cleft and peri-soma is crucial for understanding Glu-related pathology. Here, we created an electrochemical Glu sensors toolkit with spatial resolution of ∼60 nm, combining biologically engineered Glu binding protein for specifically capturing Glu together with chemically designed ferrocene groups for signal labeling. Modulation conjugation approach between GluR and ferrocene significantly improved sensitivity up to 32-folds....
Jie Liu

Type II kinase inhibitors that target Parkinson's disease-associated LRRK2

3 months 1 week ago
Increased kinase activity of leucine-rich repeat kinase 2 (LRRK2) is associated with Parkinson's disease (PD). Numerous LRRK2-selective type I kinase inhibitors have been developed, and some have entered clinical trials. Here, to our knowledge, we present the first type II kinase inhibitors that target LRRK2. Targeting the inactive conformation of LRRK2 is functionally distinct from targeting the active-like conformation using type I inhibitors. We designed these inhibitors with a combinatorial...
Nicolai D Raig

A ventral hippocampal-lateral septum pathway regulates social novelty preference

3 months 1 week ago
The ability to distinguish strangers from familiar individuals is crucial for the survival of most mammalian species. In humans, an inability to recognize kin and familiar individuals and engage in appropriate behaviors is associated with several types of dementia, including Alzheimer's disease. Mice preferentially spend more time investigating a novel individual relative to a familiar individual. Yet, how social novelty-related information drives increased investigation of the novel animal...
Maha Rashid

The reaction mechanism for glycolysis side product degradation by Parkinson's disease-linked DJ-1

3 months 1 week ago
DJ-1/PARK7 is the causative gene for hereditary recessive Parkinson's disease. Recent studies have reported that DJ-1 hydrolyzes cyclic 3-phosphoglyceric anhydride (cPGA), a highly reactive metabolite. However, the molecular mechanisms underlying cPGA hydrolase activity have yet to be fully elucidated. To gain a more comprehensive understanding of this activity in DJ-1, we performed molecular simulations that predicted how DJ-1 recognizes and hydrolyzes cPGA. The accuracy of these structural...
Aiko Watanabe

Role of LIMK1-cofilin-actin axis in dendritic spine dynamics in Alzheimer's disease

3 months 1 week ago
Dysregulation of dendritic spine dynamics, a process essential for synaptic plasticity and memory, is a hallmark of Alzheimer's disease (AD). Actin dynamics, largely regulated by the LIMK1-cofilin pathway, are central to maintaining structural and functional stability in neurons. In healthy brains, the LIMK1-cofilin-actin axis modulates actin polymerization within dendritic spines, supporting spine growth and plasticity. However, in AD, this pathway is altered, leading to both actin and synaptic...
Fabiola Paciello

High-frequency repetitive transcranial magnetic stimulation upregulates BDNF expression and promotes synaptogenesis in mouse models of Parkinson's disease

3 months 2 weeks ago
Synaptic dysfunction exists before symptoms occur in Parkinson's disease, and restoring synaptic function as a promising therapeutic approach. Brain-derived neurotrophic factor serves as a key neuroregulatory factor in regulating synaptic function. Studies have shown that the protein levels of brain-derived neurotrophic factor is low in Parkinson's disease mice. However, repetitive transcranial magnetic stimulation (rTMS) can mitigate this decline. We explored the protective role of rTMS on...
Dongdong Chen

Cell-death pathways and tau-associated neuronal vulnerability in Alzheimer's disease

3 months 2 weeks ago
Neuronal loss is the ultimate driver of neural system dysfunction in Alzheimer's disease (AD). We used single-nucleus RNA sequencing and neuropathological phenotyping to elucidate mechanisms of neurodegeneration in AD by identifying vulnerable neuronal populations and probing for their differentially expressed genes. Evidenced by transcriptomic analyses and quantitative tau immunoassays of human AD and non-AD brain tissue, we identified a neuronal population especially vulnerable to tau...
Gen Lin

Proteomic signatures of corona and herpes viral antibodies identify IGDCC4 as a mediator of neurodegeneration

3 months 2 weeks ago
Mechanisms underlying the dynamic relationships of viral infections and neurodegeneration warrant examination. Using a community-based cohort of older adults, the current study characterized the neurocognitive (cognitive functioning, brain volumes, Alzheimer's disease positron emission tomography, and plasma biomarkers) and plasma proteomic (7268 proteins) profiles of four common coronavirus and six herpesvirus antibody titers. Genetic inference techniques demonstrated the associations between...
Michael R Duggan

Thalamic free water elevation and its association with glymphatic dysfunction in Parkinson's disease: A cross-sectional and longitudinal study

3 months 2 weeks ago
Free Water (FW) is considered an indicator of neuroinflammation, while the Index of Diffusivity along the Perivascular Space (ALPS) is a recently introduced measure of glymphatic function. However, no study has yet investigated the specific relationships between these factors simultaneously. This study aimed to examine changes in FW in the thalamic midline and lateral nuclei in Parkinson's disease (PD), with a particular focus on the potential influence of glymphatic system dysfunction. MRI data...
Zhanyu Kuang

Translational disease modeling of peripheral blood identifies type 2 diabetes biomarkers predictive of Alzheimer's disease

3 months 2 weeks ago
Type 2 diabetes (T2D) is a significant risk factor for Alzheimer's disease (AD). Despite multiple studies reporting this connection, the mechanism by which T2D exacerbates AD is poorly understood. It is challenging to design studies that address co-occurring and comorbid diseases, limiting the number of existing evidence bases. To address this challenge, we expanded the applications of a computational framework called Translatable Components Regression (TransComp-R), initially designed for...
Brendan K Ball

β-synuclein blocks α-synuclein condensate fusion to disrupt the maturation of phase separation

3 months 2 weeks ago
The abnormal accumulation of α-synuclein (α-Syn) is a key feature of Parkinson's disease (PD) and other synucleinopathies. α-Syn undergoes liquid-liquid phase separation (LLPS) to accelerate the amyloid aggregation. β-synuclein (β-Syn) colocalizes with α-Syn and affects its aggregation. It remains poorly understood how the LLPS of α-Syn is regulated by β-Syn. Here, we find that β-Syn co-condenses with α-Syn, negatively regulating the LLPS of α-Syn. The mobility of α-Syn is reduced in α-Syn/β-Syn...
Bingkuan Xu

Predicting and preventing Alzheimer's disease

3 months 2 weeks ago
With all the advances in both the science of aging and artificial intelligence (AI), we are in a propitious position to accurately and precisely determine who is at high risk of developing Alzheimer's disease years before signs of even mild cognitive deficit. It takes at least 20 years for aggregates of misfolded β-amyloid and tau proteins to accumulate in the brain along with neuroinflammation that they incite. This provides a long window of opportunity to get ahead of the pathobiological...
Eric Topol
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Alzheimer and Parkinson: Latest results from PubMed
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