Parkinson's families project: a UK-wide study of early onset and familial Parkinson's disease.

The Parkinson's Families Project is a UK-wide study aimed at identifying genetic variation associated with familial and early-onset Parkinson's disease (PD). We recruited individuals with a clinical diagnosis of PD and age at motor symptom onset ≤45 years and/or a family history of PD in up to third-degree relatives. Where possible, we also recruited affected and unaffected relatives.

Apolipoprotein E aggregation in microglia initiates Alzheimer's disease pathology by seeding β-amyloidosis.

The seeded growth of pathogenic protein aggregates underlies the pathogenesis of Alzheimer's disease (AD), but how this pathological cascade is initiated is not fully understood. Sporadic AD is linked genetically to apolipoprotein E (APOE) and other genes expressed in microglia related to immune, lipid, and endocytic functions. We generated a transgenic knockin mouse expressing HaloTag-tagged APOE and optimized experimental protocols for the biochemical purification of APOE, which enabled us to identify fibrillary aggregates of APOE in mice with amyloid-β (Aβ) amyloidosis and in human AD brain autopsies.

Risk factors and clinical significance of post-stroke incident ischemic lesions.

Introduction: While incident ischemic lesions (IILs) are not unusual on follow-up magnetic resonance imaging (MRI) following stroke, their risk factors and prognostic significance remain unknown.

Methods: In a prospective multicenter study of 503 acute stroke patients, we assessed IILs on registered MRI images at baseline and 6 months, analyzing risk factors and clinical outcomes across 36 months.

Results: At 6 months, 78 patients (15.

The role of leukocytes in cognitive impairment due to long-term exposure to fine particulate matter: A large population-based mediation analysis.

Introduction: Our understanding of how fine particulate matter (PM) impacts cognitive functioning is limited. Systemic inflammation processes may play a role in mediating this effect.

Methods: This prospective cohort study used data from 66,254 participants aged 18+ between 2006 and 2015 from the Dutch Lifelines Cohort Study and Biobank.

Localization and Tumor Growth Inhibition of I-131-Labeled Monoclonal Antibody ERIC1 in a Subcutaneous Xenograft Model of Small Cell Lung Cancer in SCID Mice.

This study evaluates the efficacy of [I]I-ERIC1 in targeting and inhibiting the growth of SCLC tumors in mice, focusing on tumor accumulation and regression and potential side effects. NCAM-positive NCI-H69 SCLC cells were implanted in CB 17 SCID mice, and [I]I-ERIC1 biokinetics were measured in organs and tissues at four post-injection time points (24, 72, 96, and 120 h). The experimental series compared tumor growth, survival, and changes in blood counts among three treatment groups (1, 2, or 3 MBq) and a control group, with treatments initiated either two or five days post implantation.

Intracranial Aneurysms and Cerebral Small Vessel Disease: Is There an Association between Large- and Small-Artery Diseases?

: Intracranial aneurysms (IAs) may be connected to interactions between large and small intracranial vessels. We aimed to investigate the association between IAs and cerebral small-vessel disease (CSVD) and assess CSVD impact on IA patient management. : This retrospective study analyzed clinical data and MRI features of CSVD in 192 subarachnoid hemorrhage (SAH) patients: 136 with incidental IA, 147 with severe CSVD without SAH/IA, and 50 controls without SAH, IA, or severe CSVD.

Calculation of virtual 3D subtraction angiographies using conditional generative adversarial networks (cGANs).

Objective: Subtraction angiographies are calculated using a native and a contrast-enhanced 3D angiography images. This minimizes both bone and metal artifacts and results in a pure image of the vessels. However, carrying out the examination twice means double the radiation dose for the patient.

Chemotherapy-induced cognitive impairment and its long-term development in patients with breast cancer: results from the observational CICARO study.

Background: Chemotherapy-induced cognitive impairment (CICI) is a well-recognized side effect of breast cancer treatment. However, prospective long-term evaluations of CICI using standardized neuropsychological tests are scarce.

Patients And Methods: This prospective longitudinal cohort study investigated cognitive dysfunction and its impact on quality of life and everyday functioning in patients with breast cancer receiving first-line chemotherapy compared to patients with breast cancer without chemotherapy.

Case report: Antibodies to myelin basic protein in a podenco-crossbreed dog with seizures.

A 6-year-old female spayed Podenco-crossbreed dog was presented with an unusual type of focal impaired awareness seizures, including sensory ataxia and postictal rest. Magnetic resonance imaging examination revealed pre- and post-contrast agent T1-weighted bilateral symmetric hyperintensities in the lentiform nuclei and globus pallidus. Repeated cerebrospinal fluid sampling showed lymphocytic pleocytosis.

A scoping review of remote and unsupervised digital cognitive assessments in preclinical Alzheimer's disease.

Subtle cognitive changes in preclinical Alzheimer's disease (AD) are difficult to detect using traditional pen-and-paper neuropsychological assessments. Remote and unsupervised digital assessments can improve scalability, measurement reliability, and ecological validity, enabling the detection and monitoring of subtle cognitive change. Here, we evaluate such tools deployed in preclinical AD samples, defined as cognitively unimpaired individuals with abnormal levels of amyloid-β (Aβ), or Aβ and tau.

Proteomic Characterization of Ubiquitin Carboxyl-Terminal Hydrolase 19 Deficient Cells Reveals a Role for USP19 in the Secretion of Lysosomal Proteins.

Ubiquitin carboxyl-terminal hydrolase 19 (USP19) is a unique deubiquitinase, characterized by multiple variants generated by alternative splicing. Several variants bear a C-terminal transmembrane domain that anchors them to the endoplasmic reticulum. Other than regulating protein stability by preventing proteasome degradation, USP19 has been reported to rescue substrates from endoplasmic reticulum-associated protein degradation in a catalytic-independent manner, promote autophagy, and address proteins to lysosomal degradation via endosomal microautophagy.

The influence of age, gender and pharmacogenetic profiles on the perspective on medicines in the German EMPAR study.

Background: Pharmacogenetic testing in routine care could provide benefits for patients, doctors and statutory health insurances. Therefore, the aim of the retrospective, observational study Einfluss metabolischer Profile auf die Arzneimitteltherapiesicherheit in der Routineversorgung (EMPAR) was to analyze the relationship between pharmacogenetic profiles, the risk of adverse drug reactions, and patients' perceptions of drug therapy in 10748 adult (≥18 years) participants in Germany.

Methods: A questionnaire was used to assess views and beliefs about medicines and participants individual perception of sensitivity to drug therapies.

Sustained effect of prasinezumab on Parkinson's disease motor progression in the open-label extension of the PASADENA trial.

The Phase II trial of Anti-alpha-Synuclein Antibody in Early Parkinson's Disease (PASADENA) is an ongoing double-blind, placebo-controlled trial evaluating the safety and efficacy of prasinezumab in early-stage Parkinson's disease (PD). During the double-blind period, prasinezumab-treated individuals showed less progression of motor signs (Movement Disorders Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III) than placebo-treated individuals. We evaluated whether the effect of prasinezumab on motor progression, assessed as a change in MDS-UPDRS Part III score in the OFF and ON states, and MDS-UPDRS Part II score, was sustained for 4 years from the start of the trial.

The p.L1795F variant causes Parkinson's disease in the European population.

Pathogenic variants in the gene represent the most common cause of autosomal dominant Parkinson's disease (PD) worldwide. We identified the p.L1795F variant in 14 White/European ancestry PD patients, including two families with multiple affected carriers and seven additional affected individuals with familial PD using genotyping and sequencing data from more than 50,000 individuals through GP2, AMP-PD, PDGENEration, and CENTOGENE.

T1234: A distortion-matched structural scan solution to misregistration of high resolution fMRI data.

Purpose: High-resolution fMRI at 7T is challenged by suboptimal alignment quality between functional data and structural scans. This study aims to develop a rapid acquisition method that provides distortion-matched, artifact-mitigated structural reference data.

Methods: We introduce an efficient sequence protocol termed T1234, which offers adjustable distortions.