A large RCT in older adults showed the online Rethink My Drink program produced durable reductions in monthly alcohol consumption at 12 months but did not change global cognition.

Conditional knock-in mice expressing the dominant-negative GNAO1 G203R mutation in specific circuits reveal striatal and forebrain contributions to seizures and motor deficits, region-specific synaptic and proteomic alterations, and that caffeine treatment rescues motor abnormalities.

The paper shows DNAJC6 is downregulated in neurons and astrocytes in sporadic PD, links that loss to impaired autolysosomal, mitochondrial, phagocytic function and pro-inflammatory astrocyte phenotypes via NURR1/FOXA2 and LRRK2-related mechanisms, and demonstrates that CRISPRa-AAV9–mediated…

Arrayed CRISPR activation and knockout screens of ~4,700 mitochondria/trafficking genes identified OXR1 activation as promoting Ser129-phosphorylated α-synuclein aggregation via mitochondrial dysfunction and EMC4 ablation as reducing aggregation by enhancing ER-driven autophagic/lysosomal…

This study shows LINC-EPS is reduced in PD patient blood and models, and that LINC-EPS protects dopaminergic neurons by scaffolding PGC-1α to its promoter to boost PGC-1α transcription, improving mitochondrial function and preventing ferroptosis, with AAV-mediated LINC-EPS and the PGC-1α activator…

The study shows that chronic low-dose co-exposure to cadmium and paraquat drives mito-ROS–dependent OPA1 dysregulation, mitochondrial fragmentation, caspase-3–mediated GSDME cleavage, and dopaminergic neuron loss producing PD-like motor and cognitive deficits in mice.

The paper shows that blood and CSF mtDNA integrity measures (major-arc deletions, 7S DNA abundance, and copy number) are altered in PINK1/PRKN and early-onset idiopathic PD, detectable in prodromal converters, associated with clinical outcomes, and substantially improve group discrimination when…

The authors developed biodegradable lysosome-acidifying polymeric nanoparticles (AcNPs) that restore lysosomal pH, enhance autophagic clearance of A30P α‑synuclein, improve mitochondrial function, and rescue neuronal loss and motor deficits in cell and Drosophila PD models.

In a multicenter cohort of 598 PD patients, blood ferroptosis markers—particularly 4-HNE—along with ferritin, selenium and ACSL4 SNPs correlated with baseline disability and one-year motor progression, supporting a link between ferroptosis and disease worsening.

This study builds and externally validates logistic models using easily obtainable clinical variables (UPSIT smell percentiles, constipation, sex, and LRRK2/GBA status) to accurately predict CSF alpha-synuclein SAA positivity in PD-enriched cohorts (AUROC 0.92–0.98).

This study demonstrates that an alpha-synuclein seed amplification assay applied to routine clinical CSF samples reliably detects Lewy body pathology and aligns well with clinical diagnoses of Parkinson's disease and dementia with Lewy bodies.

Wdfy3 haploinsufficiency in mice impairs selective autophagy and produces proteomic and histological signatures that overlap presymptomatic Parkinson's disease, particularly in cortex and substantia nigra.

This study presents a semi-automated 3D volumetric immunofluorescence quantification method for intraneural S129 phospho-α-synuclein in skin biopsies that discriminates synucleinopathies (PD/MSA) from PSP with high AUC, sensitivity and specificity in a small cohort.

Using Mendelian randomization in large European samples, the study implicates specific plasma lipids (e.g., triacylglycerol and phosphatidylcholine as protective; sphingomyelin as pathogenic), two trace elements (selenium protective; an unexpected iridium signal), and CSF metabolites (including…

This review surveys AI/ML approaches for discovering and validating molecular, imaging, and digital biomarkers related to motor dysfunction across PD, HD, ALS, and SCAs—highlighting candidates such as alpha-synuclein, tau, and neurofilament light chain and the promise of multimodal models while…

This study establishes a refined chronic low-dose MPTP/probenecid regimen in mature adult mice that yields progressive motor and cognitive impairments, sustained loss of tyrosine hydroxylase-positive neurons, and phosphorylated α-synuclein aggregation while preserving high survival for longitudinal…

Combines CatWalk gait analysis and DeepLabCut markerless pose estimation in L61 α‑synuclein mice to generate sensitive, complementary motor endpoints (tail‑base lateral variance and hind base of support) that distinguish transgenic from control animals at 12 and 18 months.

The study reports elevated urine 22:6-BMP in PSP that correlates with CSF total LRRK2, shows that a PD-linked LRRK2 variant associates with higher CSF LRRK2, and that baseline monocyte LRRK2 predicts 1‑year clinical decline, supporting LRRK2 and lysosomal biomarkers in PSP.

Combined analysis of skin morphometry (reduced α-syn–positive fibers, increased collagen IV staining and α-syn–positive melanocytes) plus salivary α-syn oligomers discriminates Parkinson's patients from controls and correlates with clinical scores.

The paper shows that circ-find-0001774 sponges miR-153-3p to boost Wnt/β-catenin signaling, lowering autophagy/apoptosis and improving dopaminergic neuron survival and motor behavior in MPP+/MPTP PD models.

Using explainable radiomic features from standard T1/T2 MRI in basal ganglia and ventral midbrain, the study accurately discriminates PD, SWEDD, and healthy controls (macro-AUC 0.85) and highlights ventral midbrain texture heterogeneity and thalamic contrast as top predictors.

Using resting-state fNIRS and graph-theory, the study found that Parkinson's patients with wearing-off exhibit a less efficient cortical network (reduced clustering and global efficiency, increased path length) with nodal abnormalities in premotor and somatosensory cortices, and that global…

Autoradiographic [18F]nifene binding to α4β2* nicotinic acetylcholine receptors is markedly increased in the hippocampus–subiculum of postmortem Parkinson's disease brains compared with controls, with noted sex- and age-related differences.

Introduces Decomposed Transfer Entropy (DTE) to separate phase, spectral amplitude, and interaction contributions to directed EEG connectivity and shows PD patients off medication exhibit a phase-dominant reweighting from frontal midline (Fz) that shifts toward healthy patterns with dopaminergic…

This review synthesizes evidence that neurovascular unit (NVU) and blood–brain barrier (BBB) dysfunction driven by immune mechanisms and disease-specific insults (e.g., α-synuclein in PD) contributes to neuroinflammation and neuronal injury across neurodegenerative diseases.