Skip to main content

Alzheimer & Parkinson

Comorbid Alzheimer's Disease and Type 2 Diabetes Microbiota Shape Age-Associated Gut-Brain Axis Profiles

19 hours 19 minutes ago
Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) share metabolic and inflammatory mechanisms, potentially mediated by the gut microbiota, yet the neurobiological impact of comorbid AD+T2DM microbiota from elderly donors remains unexplored. Fecal microbiota from healthy, AD, T2DM, and AD+T2DM postmenopausal female donors (aged 56-89 years) was transplanted into antibiotic-treated male mice. Behavioral testing, blood profiling, hippocampal neurotrophic gene expression, and 16S rRNA...
Alessandro Atzeni

SpaNiche: spatial niche analysis to explore colocalization patterns and cellular interactions in spatial transcriptomics data

19 hours 19 minutes ago
We propose a computational framework for spatial niche analysis (SpaNiche) in spatial transcriptomics data to uncover colocalization patterns and infer potential ligand-receptor interactions. SpaNiche leverages graph-regularized joint non-negative matrix factorization to integrate information from cell abundance and ligand-receptor expression, identifying spatial colocalization patterns among cell types while providing insights into associated ligand-receptor interactions. Besides, SpaNiche...
Siyuan Huang

GWAS meta-analysis of cerebrospinal fluid Alzheimer's biomarkers reveals loci regulating lipids, brain volume and autophagy

1 day 19 hours ago
Cerebrospinal fluid amyloid beta 42, total tau, and phosphorylated tau 181 are well accepted markers of Alzheimer's disease. These biomarkers better reflect disease pathogenesis compared to clinical diagnosis. Here, we perform a genome wide association study meta-analysis including 18,948 individuals of European ancestry and identify 12 genome-wide significant loci across all three biomarkers, eight of them novel. We replicate the association of biomarkers with APOE, CR1, GMNC/CCDC50 and...
Jigyasha Timsina

CK2 inhibition suppresses glial inflammation in models of neuroinflammation and neurodegeneration

1 day 19 hours ago
Neuroinflammation plays a key role in Alzheimer's disease (AD) and many other neurodegenerative disorders. Chronic activation of astrocytes and microglia fuels neuronal damage via cytokine secretion, oxidative stress, and proteolysis, yet glial inflammatory regulation remains poorly understood. Using chemoproteomics, we identified CK2, particularly the brain-enriched catalytic subunit CK2α2, as a key driver of astrocytic inflammation. CK2 enhances NF-κB activity by phosphorylating NF-κB S529 and...
Ioana I N Da Silva

Mild cognitive impairment cases affect the predictive power of Alzheimer's disease diagnostic models using routine clinical variables

1 day 19 hours ago
Diagnostic models using primary care routine clinical variables have been limited in their ability to identify Alzheimer's disease (AD) patients. In this study, we sought to better understand the effect of mild cognitive impairment (MCI) on the predictive performance of AD diagnostic models. We sourced data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. CatBoost was used to assess the utility of routine clinical variables that are accessible to primary care physicians, such...
Caitlin A Finney

Neurons of the human subthalamic nucleus engage with local delta frequency processes during action cancellation

1 day 19 hours ago
The subthalamic nucleus (STN) is a critical hub for inhibitory control, implicated in decision making under conflict and impulsivity. Delta frequency oscillations have also been associated with inhibitory control processes, yet the relationship between human STN neuronal activity and local delta frequencies during response inhibition remains unresolved. Here we recorded STN neurons and local field potentials in patients with Parkinson's disease performing a stop-signal reaction time task during...
Johanna Petra Szabó

The temperature dependence of amyloid <em>β</em> solubility reveals the hydrophobic effect as the main driving force for fibril formation

2 days 19 hours ago
The aggregation of amyloid proteins into fibrillar and oligomeric aggregates is linked to a number of neurodegenerative diseases. While the disease onset remains elusive in many cases, an understanding of the driving forces for the aggregation may help finding possible causes. While effects on amyloid formation kinetics are more commonly studied, gaining insights into these driving forces require a thermodynamic approach with equilibrium measurements. Here we investigate the temperature...
Max Lindberg

Dopaminergic modulation of the sense of agency influences moral behavior in Parkinson's disease

2 days 19 hours ago
Embodied accounts of morality propose that corporeal self-awareness helps restrain immoral actions. The Sense of Agency (SoA)-the feeling of controlling one's actions and their consequences-drops when individuals harm others. However, whether modulating SoA shifts moral behavior remains unclear. Parkinson's Disease (PD) offers a unique model to address this question, because dopaminergic dysfunction affects both SoA and moral decision-making. We tested 23 individuals with PD in ON and OFF...
Giorgia Ponsi

Cohort profile Davos Alzheimer's Collaborative DAC Egypt Cohort

2 days 19 hours ago
The Davos Alzheimer's Collaborative (DAC) Egypt Cohort (DAC-Egypt) is a newly established longitudinal study of cognitive aging in a community-based convenience sample of older Egyptian adults. The cohort's purpose is to characterize trajectories of cognitive decline and dementia risk factors in an understudied population, filling a critical gap in aging research in the Middle East. Participants (n = 1,530) aged 55 and above were recruited via regionally diverse convenience sampling, with...
Sara A Moustafa

Microbiome signature of Parkinson's disease in healthy and genetically at-risk individuals

2 days 19 hours ago
Parkinson's disease (PD) is a major cause of disability. GBA1 variants are the most common genetic risk factor for PD and increase the risk up to 30-fold. Why only approximately 20% of GBA1 variant carriers develop PD remains unknown. Here, by combining clinical and fecal metagenomics data from 271 patients with PD, from 43 carriers of GBA1 variants not manifesting PD symptoms (GBA-NMC) and from 150 healthy controls, and using an innovative microbiome analysis, combining differential abundance...
Elisa Menozzi

Cryo-EM structures of anti Z-DNA antibodies in complex with antigen reveal distinct recognition modes of a left-handed geometry

2 days 19 hours ago
Double-stranded nucleic acids can undergo transitions from canonical B/A-forms to alternate left-handed Z-DNA/Z-RNA (Z-NAs). Z-NAs are implicated in processes such as neuroinflammation in Alzheimer's disease, Lupus Erythematosus, microbial biofilms, and type I interferon-mediated human pathologies. Since endogenous Z-NA sensors like the Zα domain can induce B-to-Z transitions, monoclonal antibodies (mAbs) Z-D11 and Z22 have been regarded as conformation-specific tools to confirm Z-NA in situ,...
Danielle Chin

Neuronal vulnerability in Parkinson's disease: insights from murine alpha-synuclein pathology models

3 days 19 hours ago
Parkinson's disease (PD) is characterised by the progressive degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). Lewy bodies- the defining neuropathological hallmark of PD-are chiefly composed of aggregated forms of α-synuclein (α-syn). Despite the widespread presence of α-syn pathology, neurodegeneration is often selective, and the mechanisms underlying the vulnerability of specific neuronal populations in PD remain poorly understood. This review critically...
Ziba Asadpoordezaki

The protective effect of biochanin A on LPS/TNF-α-induced PD models is exerted by regulating ferroptosis through the Sirt1/Nrf2/GPX4 signaling pathway

4 days 19 hours ago
Ferroptosis promotes the progression of Parkinson's disease (PD) through its unique regulatory pathways. Biochanin A (Bioch A) has long attracted the attention of researchers due to its neuroprotective effects. However, whether Bioch A can treat PD by inhibiting ferroptosis and the underlying mechanism remain unclear. This study aimed to investigate whether Bioch A exerts a neuroprotective effect on PD by activating the Sirt1/Nrf2/GPX4 signaling pathway to inhibit ferroptosis. Behavior was...
Han Yang

SARM1 executes neuronal parthanatos and promotes excitotoxic cell death

5 days 19 hours ago
The nicotinamide adenine dinucleotide (NAD^(+)) hydrolase sterile alpha and Toll/interleukin-1 receptor motif-containing 1 (SARM1) is the central executioner of pathological axon degeneration and is allosterically activated by an increased nicotinamide mononucleotide (NMN)/NAD^(+) ratio. DNA damage induces NAD^(+) loss and an increased NMN/NAD^(+) ratio by hyperactivating poly(ADP-ribose) polymerase 1 (PARP1), which triggers the parthanatos cell death pathway. Multiple mechanistically distinct...
Tong Wu

Molecular mechanisms of PINK1/Parkin-mediated mitochondrial quality control

5 days 19 hours ago
PINK1/Parkin-mediated mitophagy and other related mitochondrial quality control pathways are critical to maintaining cellular homeostasis and neuronal health, and indeed, mutations in PINK1 and PRKN that disrupt this pathway cause early-onset Parkinson's disease. While PINK1-dependent Parkin recruitment to damaged mitochondria has been established for over a decade, recent structural and biochemical advances have illuminated the mechanisms governing their allosteric activation and integration...
Andrew N Bayne

Dysfunction of the episodic memory network in the Alzheimer's disease cascade

5 days 19 hours ago
Alzheimer's disease (AD) is a major cause of dementia and cognitive decline. Here, we assessed how episodic memory (EM) network dysfunction, a hallmark of AD, is related to the longitudinal progression of AD biomarkers, neurodegeneration and cognition using data from the DZNE DELCODE study. This data set includes over 1000 longitudinal functional magnetic resonance imaging measurements of EM network function. We related activation and deactivation of EM to individual disease progression scores...
René Lattmann

Electromagnetic field-inducible in vivo gene switch for remote spatiotemporal control of gene expression

1 week ago
Gaining precise control of gene expression is crucial in biomedical applications. However, spatiotemporal precision remains challenging. Here, we present a remotely controlled in vivo gene switch responsive to electromagnetic fields (EMFs) that enables precise spatiotemporal activation of target genes. We uncovered the EMF-inducible gene switch activation mechanism via a CRISPR-Cas9 screen, identifying cytochrome b5 type B (Cyb5b) as an essential mediator likely acting as an EMF sensor. The...
Junyeop Kim

Single-nucleus brain transcriptomics reveals microglia dysfunction in multiple system atrophy

1 week ago
Multiple system atrophy (MSA) is a rare, age-related neurodegenerative disease that shares clinical and pathological features with Parkinson's disease (PD) but presents a more devastating disease course. To elucidate the distinct cellular pathophysiology, we performed single-nucleus RNA sequencing on postmortem striatal brain tissue from 7 MSA and 12 PD patients, and 10 non-neurological cases. Here, we show significant compositional differences in astroglia and microglia subtypes, while...
Rasmus Rydbirk

Variants in the proteasome regulator PSMF1 cause a phenotypic spectrum from parkinsonism to perinatal lethality

1 week ago
Dissecting biological pathways highlighted by Mendelian gene discovery has provided critical insights into the pathogenesis of Parkinson's disease (PD) and neurodegeneration. This approach ultimately catalyzes the identification of potential biomarkers and therapeutic targets. Here we identify PSMF1 as a gene implicated in parkinsonism and childhood neurodegeneration. We find that biallelic PSMF1 missense and loss-of-function variants co-segregate with phenotypes from early-onset PD to perinatal...
Francesca Magrinelli
Checked
3 hours 10 minutes ago
Alzheimer and Parkinson: Latest results from PubMed
Subscribe to Alzheimer & Parkinson feed