Age, Sex, and Anatomical Location Patterns in Cutaneous Pyogenic Granuloma Cases.

Importance: Cutaneous pyogenic granulomas (PGs) are commonly encountered, benign, vascular tumors, in which epidemiologic factors have been variably reported, in part, due to sample size limitations and a focus on either adult or pediatric patients.

Objective: To assemble a large dataset of pathologically diagnosed PGs across the continuum of age and investigate patterns of PGs by demographic factors, including age, sex, and anatomical location.

Design, Setting, And Participants: This retrospective case series included case reports of patients with pathologically confirmed PGs of cutaneous origin reported between April 1, 2010, to March 31, 2020.

Metabolomic and lipidomic signatures in autosomal dominant and late-onset Alzheimer's disease brains.

Introduction: The identification of multiple genetic risk factors for Alzheimer's disease (AD) suggests that many pathways contribute to AD onset and progression. However, the metabolomic and lipidomic profiles in carriers of distinct genetic risk factors are not fully understood. The metabolome can provide a direct image of dysregulated pathways in the brain.

Genomic atlas of the proteome from brain, CSF and plasma prioritizes proteins implicated in neurological disorders.

Understanding the tissue-specific genetic controls of protein levels is essential to uncover mechanisms of post-transcriptional gene regulation. In this study, we generated a genomic atlas of protein levels in three tissues relevant to neurological disorders (brain, cerebrospinal fluid and plasma) by profiling thousands of proteins from participants with and without Alzheimer's disease. We identified 274, 127 and 32 protein quantitative trait loci (pQTLs) for cerebrospinal fluid, plasma and brain, respectively.

Functional genomic analyses uncover APOE-mediated regulation of brain and cerebrospinal fluid beta-amyloid levels in Parkinson disease.

Alpha-synuclein is the main protein component of Lewy bodies, the pathological hallmark of Parkinson's disease. However, genetic modifiers of cerebrospinal fluid (CSF) alpha-synuclein levels remain unknown. The use of CSF levels of amyloid beta, total tau, and phosphorylated tau as quantitative traits in genetic studies have provided novel insights into Alzheimer's disease pathophysiology.

Examination of the Effect of Rare Variants in TREM2, ABI3, and PLCG2 in LOAD Through Multiple Phenotypes.

Background: Rare variants in PLCG2 (p.P522R), ABI3 (p.S209F), and TREM2 (p.

Correction to: Overlapping genetic architecture between Parkinson disease and melanoma.

The original version of this article unfortunately contained a mistake. Supplementary Tables 3 and 4 are not available with the rest of the supplementary material available online.

Well Water and Parkinson's Disease in Medicare Beneficiaries: A Nationwide Case-Control Study.

Background: Well water frequently is considered a risk factor for Parkinson's disease (PD), but few studies were designed appropriately to test whether geographic factors affect PD risk.

Objective: To determine the risk of PD in relation to residential use of private well water.

Methods: In a nationwide, population-based case-control study, we identified all incident PD cases (N = 89,790) and all comparable controls (N = 21,549,400) age 66-90 who solely relied on Medicare coverage in the U.

genotype regulates pathology and disease progression in synucleinopathy.

Apolipoprotein E () ε4 genotype is associated with increased risk of dementia in Parkinson's disease (PD), but the mechanism is not clear, because patients often have a mixture of α-synuclein (αSyn), amyloid-β (Aβ), and tau pathologies. ε4 exacerbates brain Aβ pathology, as well as tau pathology, but it is not clear whether genotype independently regulates αSyn pathology. In this study, we generated A53T αSyn transgenic mice (A53T) on knockout (A53T/EKO) or human knockin backgrounds (A53T/E2, E3, and E4).

Overlapping genetic architecture between Parkinson disease and melanoma.

Epidemiologic studies have reported inconsistent results regarding an association between Parkinson disease (PD) and cutaneous melanoma (melanoma). Identifying shared genetic architecture between these diseases can support epidemiologic findings and identify common risk genes and biological pathways. Here, we apply polygenic, linkage disequilibrium-informed methods to the largest available case-control, genome-wide association study summary statistic data for melanoma and PD.

An atlas of cortical circular RNA expression in Alzheimer disease brains demonstrates clinical and pathological associations.

Parietal cortex RNA-sequencing (RNA-seq) data were generated from individuals with and without Alzheimer disease (AD; n = 13; n = 83) from the Knight Alzheimer Disease Research Center (Knight ADRC). Using this and an independent (Mount Sinai Brain Bank (MSBB)) AD RNA-seq dataset, cortical circular RNA (circRNA) expression was quantified in the context of AD. Significant associations were identified between circRNA expression and AD diagnosis, clinical dementia severity and neuropathological severity.

The TMEM106B FTLD-protective variant, rs1990621, is also associated with increased neuronal proportion.

Apart from amyloid β deposition and tau neurofibrillary tangles, Alzheimer's disease (AD) is a neurodegenerative disorder characterized by neuronal loss and astrocytosis in the cerebral cortex. The goal of this study is to investigate genetic factors associated with the neuronal proportion in health and disease. To identify cell-autonomous genetic variants associated with neuronal proportion in cortical tissues, we inferred cellular population structure from bulk RNA-Seq derived from 1536 individuals.

The gene cluster is a key modulator of soluble TREM2 and Alzheimer's disease risk.

Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) has been associated with Alzheimer's disease (AD). TREM2 plays a critical role in microglial activation, survival, and phagocytosis; however, the pathophysiological role of sTREM2 in AD is not well understood. Understanding the role of sTREM2 in AD may reveal new pathological mechanisms and lead to the identification of therapeutic targets.

A single-nuclei RNA sequencing study of Mendelian and sporadic AD in the human brain.

Background: Alzheimer's disease (AD) is the most common form of dementia. This neurodegenerative disorder is associated with neuronal death and gliosis heavily impacting the cerebral cortex. AD has a substantial but heterogeneous genetic component, presenting both Mendelian and complex genetic architectures.

Overlap in the Genetic Architecture of Stroke Risk, Early Neurological Changes, and Cardiovascular Risk Factors.

Background and Purpose- The genetic relationships between stroke risk, stroke severity, and early neurological changes are complex and not completely understood. Genetic studies have identified 32 all stroke risk loci. Polygenic risk scores can be used to compare the genetic architecture of related traits.

TREM2 brain transcript-specific studies in AD and TREM2 mutation carriers.

Background: Low frequency coding variants in TREM2 are associated with Alzheimer disease (AD) risk and cerebrospinal fluid (CSF) TREM2 protein levels are different between AD cases and controls. Similarly, TREM2 risk variant carriers also exhibit differential CSF TREM2 levels. TREM2 has three different alternative transcripts, but most of the functional studies only model the longest transcript.

Integrative system biology analyses of CRISPR-edited iPSC-derived neurons and human brains reveal deficiencies of presynaptic signaling in FTLD and PSP.

Mutations in the microtubule-associated protein tau (MAPT) gene cause autosomal dominant frontotemporal lobar degeneration with tau inclusions (FTLD-tau). MAPT p.R406W carriers present clinically with progressive memory loss and neuropathologically with neuronal and glial tauopathy.

Genetic variants associated with Alzheimer's disease confer different cerebral cortex cell-type population structure.

Background: Alzheimer's disease (AD) is characterized by neuronal loss and astrocytosis in the cerebral cortex. However, the specific effects that pathological mutations and coding variants associated with AD have on the cellular composition of the brain are often ignored.

Methods: We developed and optimized a cell-type-specific expression reference panel and employed digital deconvolution methods to determine brain cellular distribution in three independent transcriptomic studies.

Use of medical care biases associations between Parkinson disease and other medical conditions.

Objective: To examine how use of medical care biases the well-established associations between Parkinson disease (PD) and smoking, smoking-related cancers, and selected positively associated comorbidities.

Methods: We conducted a population-based, case-control study of 89,790 incident PD cases and 118,095 randomly selected controls, all Medicare beneficiaries aged 66 to 90 years. We ascertained PD and other medical conditions using ICD-9-CM codes from comprehensive claims data for the 5 years before PD diagnosis/reference.

Pleiotropic Effects of Variants in Dementia Genes in Parkinson Disease.

The prevalence of dementia in Parkinson disease (PD) increases dramatically with advancing age, approaching 80% in patients who survive 20 years with the disease. Increasing evidence suggests clinical, pathological and genetic overlap between Alzheimer disease, dementia with Lewy bodies and frontotemporal dementia with PD. However, the contribution of the dementia-causing genes to PD risk, cognitive impairment and dementia in PD is not fully established.

Parkinson disease polygenic risk score is associated with Parkinson disease status and age at onset but not with alpha-synuclein cerebrospinal fluid levels.

Background: The genetic architecture of Parkinson's Disease (PD) is complex and not completely understood. Multiple genetic studies to date have identified multiple causal genes and risk loci. Nevertheless, most of the expected genetic heritability remains unexplained.

Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease.

Alzheimer disease (AD), Frontotemporal lobar degeneration (FTD), Amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD) have a certain degree of clinical, pathological and molecular overlap. Previous studies indicate that causative mutations in AD and FTD/ALS genes can be found in clinical familial AD. We examined the presence of causative and low frequency coding variants in the AD, FTD, ALS and PD Mendelian genes, in over 450 families with clinical history of AD and over 11,710 sporadic cases and cognitive normal participants from North America.

TMEM230 in Parkinson's disease.

A study on familial Parkinson disease (PD) described 4 variants in the gene TMEM230 (Chr. 20p13) as the cause of PD. The aim of this study was to test if variants in the TMEM230 gene are associated with PD in 2 independent American European data sets.

Species-dependent posttranscriptional regulation of NOS1 by FMRP in the developing cerebral cortex.

Fragile X syndrome (FXS), the leading monogenic cause of intellectual disability and autism, results from loss of function of the RNA-binding protein FMRP. Here, we show that FMRP regulates translation of neuronal nitric oxide synthase 1 (NOS1) in the developing human neocortex. Whereas NOS1 mRNA is widely expressed, NOS1 protein is transiently coexpressed with FMRP during early synaptogenesis in layer- and region-specific pyramidal neurons.