Biology subjects

Dawson, T.

Publications and source records attributed to Dawson, T..

34 records · Page 2Linked to original sources

bioRxiv2024

Life stage impact on the human skin ecosystem: lipids and the microbial community

While research into gut-microbe interactions is common and advanced, with multiple defined impacts on human health, studies exploring the significance of skin-microbe interactions remain underrepresented. Skin is the largest human organ, has a vast surface area, and is inhabited by a plethora of microorganisms which metabolise sebaceous lipids. Sebaceous free fatty acids are metabolized into bioactive lipid mediators with immune-modulatory properties by skin-resident microbes, including Malassezia. Intriguingly, many of the same lipid mediators are also found on human skin, implying these compounds may have microbial or mixed microbial/human origin. To support this hypothesis, we isolated lipids and microbial DNA from the skin of prepubescent, adult, pre- and post-menopausal volunteers and performed correlational analyses using skin lipidomics and metagenomics to compare lipid mediator profiles and microbiome compositions on skin with either low or high sebaceous gland activity. We found that specific microbial taxonomies were positively and negatively correlated with skin lipid mediator species with high statistical significance. 2D in vitro co-cultures with Malassezia and keratinocytes also directly linked the production of specific lipid mediators, detected on healthy human skin, to secretion of immuno-stimulatory cytokines. Together, these findings further support the hypothesis that microbial-derived skin lipid mediators influence healthy skin homeostasis and skin disease development and progression, thereby spotlighting the relevance of the skin microbiomes footprint on human health.

microbiology↗

bioRxiv2023

Defects in Mitochondrial Biogenesis Drive Mitochondrial Alterations in PINK1-deficient Human Dopamine Neurons

Mutations and loss of activity in the protein kinase PINK1 play a role in the pathogenesis of Parkinsons disease (PD). PINK1 regulates many aspects of mitochondrial quality control including mitochondrial autophagy (mitophagy), fission, fusion, transport, and biogenesis. Defects in mitophagy are though to play a predominant role in the loss of dopamine (DA) neurons in PD. Here we show that, although there are defects in mitophagy in human DA neurons lacking PINK1, mitochondrial deficits induced by the absence of PINK1 are primarily due to defects in mitochondrial biogenesis. Upregulation of PARIS and the subsequent down regulation of PGC-1 accounts for the mitochondrial biogenesis defects. CRISPR/Cas9 knockdown of PARIS completely restores the mitochondrial biogenesis defects and mitochondrial function without impacting the deficits in mitophagy due to the absence of PINK1. These results highlight the importance mitochondrial biogenesis in the pathogenesis of PD due to inactivation or loss of PINK1 in human DA neurons.

neuroscience↗

bioRxiv2023

Histone H1.2 Dependent Translocation of Poly (ADP-ribose) Initiates Parthanatos

Toxic cellular insults activate the nuclear protein poly (ADP-ribose) (PAR) polymerase-1 (PARP-1) to initiate parthanatos, a regulated cell death program. PAR acts as a death signal by translocating from the nucleus to the cytosol, where it activates the next steps in the parthanatic cell death cascade. How PAR translocates from the nucleus to the cytosol is not known. Here we show that PARylation and PAR binding to histone H1.2 enables it to act as a carrier, transporting PAR out of the nucleus to the cytosol. Knocking down the expression of histone H1.2 via CRISPR/Cas9 and knockout of histone H1.2 reduces the translocation of PAR to the cytosol after treatment of human cortical neurons with N-methyl-D-aspartate (NMDA) or following oxygen-glucose deprivation (OGD). The PAR-dependent E3 ubiquitin ligase, Iduna (RNF146) ubiquitinates PARylated H1.2. Overexpression of Iduna reduces the expression levels of cytosolic histone H1.2, preventing the translocation of PAR following NMDA or OGD exposure, similar to inhibition of PAR formation by the PARP inhibitor, DPQ. Whereas, the catalytically null variant Iduna C60A, or the PAR binding mutant Iduna Y156A and R157A (YRAA) was ineffective in ubiquitinating histone H1.2 and preventing the reduction in cytosolic histone H1.2 levels and PAR translocation from the nucleus to the cytosol. Histone H1.2 heterozygote and homozygote knockout mice exhibited reduced infarct volume 24 hrs post middle cerebral artery occlusion (MCAO) and showed better recovery in motor deficits than wildtype littermates at day 3 and/or day 7 post MCAO. Collectively, these findings reveal histone H1.2 as the key carrier of PAR out of the nucleus to the cytosol where it participates in the next step of the parthanatic cell death cascade.

cell biology↗

bioRxiv2023

Pathological Tau transmission initiated by binding lymphocyte-activation gene 3

The spread of prion-like protein aggregates is believed to be a common driver of pathogenesis in many neurodegenerative diseases. Accumulated tangles of filamentous Tau protein are considered pathogenic lesions of Alzheimers disease (AD) and related Tauopathies, including progressive supranuclear palsy, and corticobasal degeneration. Tau pathologies in these illnesses exhibits a clear progressive and hierarchical spreading pattern that correlates with disease severity1, 2. Clinical observation combined with complementary experimental studies3, 4 have shown that Tau preformed fibrils (PFF) are prion-like seeds that propagate pathology by entering cells and templating misfolding and aggregation of endogenous Tau. While several receptors of Tau are known, they are not specific to the fibrillar form of Tau. Moreover, the underlying cellular mechanisms of Tau PFF spreading remains poorly understood. Here, we show that the lymphocyte-activation gene 3 (Lag3) is a cell surface receptor that binds to PFF, but not monomer, of Tau. Deletion of Lag3 or inhibition of Lag3 in primary cortical neurons significantly reduces the internalization of Tau PFF and subsequent Tau propagation and neuron-to-neuron transmission. Propagation of Tau pathology and behavioral deficits induced by injection of Tau PFF in the hippocampus and overlying cortex are attenuated in mice lacking Lag3 selectively in neurons. Our results identify neuronal Lag3 as a receptor of pathologic Tau in the brain, and for AD and related Tauopathies a therapeutic target. One Sentence SummaryLag3 is a neuronal receptor specific for Tau PFF, and is required for uptake, propagation and transmission of Tau pathology.

neuroscience↗

bioRxiv2023

Flowers are leakier than leaves but cheaper to build

- Producing and maintaining flowers is essential for reproduction in most angiosperms, underpinning population persistence and speciation. Although the physiological costs of flowers often oppose pollinator selection, these physiological costs have rarely been quantified. - We measured a suite of physiological traits quantifying the water and carbon costs and drought tolerance on flowers and leaves of over 100 phylogenetically diverse species, including water and dry mass contents, minimum epidermal conductance to water vapor (gmin), vein density, and dry mass per area. - Although there was substantial variation among species, flowers had significantly higher gmin and water content per unit area than leaves, but significantly lower vein density and dry mass per area than leaves. Both leaves and flowers exhibited similarly strong scaling between dry mass investment and water content. - The higher gmin of flowers offset their higher water content, suggesting that flowers may desiccate more rapidly than leaves during drought. The coordination between dry mass and water investment suggests that flowers rely on a hydrostatic skeleton to remain upright rather than on a carbon-based skeleton. For short-lived structures like flowers, water may be relatively cheaper than carbon, particularly given the relatively high amount of water loss per unit of carbon synthesized in photosynthesis.

plant biology↗

bioRxiv2023

Gut-associated lymphoid tissue attrition associates with response to anti-α4β7 therapy in ulcerative colitis

Targeting the 4{beta}7-MAdCAM-1 axis with vedolizumab (VDZ) is a front-line therapeutic paradigm in ulcerative colitis (UC). However, mechanism(s) of action (MOA) of VDZ remain relatively undefined. Here, we examined three distinct cohorts of patients with UC (n=83, n=60, and n=21), to determine the effect of VDZ on the mucosal and peripheral immune system. Transcriptomic studies with protein level validation were used to study drug MOA using conventional and transgenic murine models. We found a significant decrease in colonic and ileal naive B and T cells and circulating gut-homing plasmablasts ({beta}7+) in VDZ-treated patients, pointing to gut-associated lymphoid tissue (GALT) targeting by VDZ. Murine Peyers patches (PP) demonstrated a significant loss cellularity associated with reduction in follicular B cells, including a unique population of epithelium-associated B cells, following anti-4{beta}7 antibody (mAb) administration. Photoconvertible (KikGR) mice unequivocally demonstrated impaired cellular entry into PPs in anti-4{beta}7 mAb treated mice. In VDZ-treated, but not anti-tumor necrosis factor-treated UC patients, lymphoid aggregate size was significantly reduced in treatment responders compared to non-responders, with an independent validation cohort further confirming these data. GALT targeting represents a novel MOA of 4{beta}7-targeted therapies, with major implications for this therapeutic paradigm in UC, and for the development of new therapeutic strategies.

immunology↗

bioRxiv2022

Intratumoral mregDC and CXCL13 T helper niches enable local differentiation of CD8 T cells following PD-1 blockade

Here, we leveraged a large neoadjuvant PD-1 blockade trial in patients with hepatocellular carcinoma (HCC) to search for correlates of response to immune checkpoint blockade (ICB) within T cell-rich tumors. We show that ICB response correlated with the clonal expansion of intratumoral CXCL13+ CH25H+ IL-21+ PD-1+ CD4 T helper cells (CXCL13+ Th) and Granzyme K+ PD-1+ effector-like CD8 T cells, whereas terminally exhausted CD39hi TOXhi PD-1hi CD8 T cells dominated in non-responders. Strikingly, most T cell receptor (TCR) clones that expanded post-treatment were found in pre-treatment biopsies. Notably, PD-1+ TCF-1+ progenitor-like CD8 T cells were present in tumors of responders and non-responders and shared clones mainly with effector-like cells in responders or terminally differentiated cells in non-responders, suggesting that local CD8 T cell differentiation occurs upon ICB. We found that these progenitor CD8 T cells interact with CXCL13+ Th cells within cellular triads around dendritic cells enriched in maturation and regulatory molecules, or "mregDC". Receptor-ligand analysis revealed unique interactions within these triads that may promote the differentiation of progenitor CD8 T cells into effector-like cells upon ICB. These results suggest that discrete intratumoral niches that include mregDC and CXCL13+ Th cells control the differentiation of tumor-specific progenitor CD8 T cell clones in patients treated with ICB.

immunology↗

bioRxiv2022

Shift of lung macrophage composition is associated with COVID-19 disease severity and recovery

Though it has been 2 years since the start of the Coronavirus Disease 19 (COVID-19) pandemic, COVID-19 continues to be a worldwide health crisis. Despite the development of preventive vaccines, very little progress has been made to identify curative therapies to treat COVID-19 and other inflammatory diseases which remain a major unmet need in medicine. Our study sought to identify drivers of disease severity and death to develop tailored immunotherapy strategies to halt disease progression. Here we assembled the Mount Sinai COVID-19 Biobank which was comprised of ~600 hospitalized patients followed longitudinally during the peak of the pandemic. Moderate disease and survival were associated with a stronger antigen (Ag) presentation and effector T cell signature, while severe disease and death were associated with an altered Ag presentation signature, increased numbers of circulating inflammatory, immature myeloid cells, and extrafollicular activated B cells associated with autoantibody formation. Strikingly, we found that in severe COVID-19 patients, lung tissue resident alveolar macrophages (AM) were not only severely depleted, but also had an altered Ag presentation signature, and were replaced by inflammatory monocytes and monocyte-derived macrophages (MoM{Phi}). Notably, the size of the AM pool correlated with recovery or death, while AM loss and functionality were restored in patients that recovered. These data therefore suggest that local and systemic myeloid cell dysregulation is a driver of COVID-19 severity and that modulation of AM numbers and functionality in the lung may be a viable therapeutic strategy for the treatment of critical lung inflammatory illnesses.

immunology↗

bioRxiv2021

Multimodal Single-Cell Characterization of the Human Granulocyte Lineage

High throughput single cell transcriptomics (scRNA-seq) has been successfully applied to characterize immune cell heterogeneity across a diverse range of settings; however, analysis of human granulocytes remains a significant challenge due to their low gene expression transcript detection. Consequently, granulocytes are typically either absent or highly under-represented and inaccurately enumerated in most human scRNA-seq datasets. Here, we apply multi-modal CITE-seq profiling to characterize granulocytes in human whole blood and bone marrow, and we show that these populations can be accurately detected and analyzed using the antibody-based modality, and that their frequencies and phenotype align well with antibody-based characterization of the same samples using CyTOF. These analyses also clearly highlight extremely low gene transcript detection across the entire granulocyte lineage including the earliest neutrophil progenitor populations when using the 10X Genomics platform. By contrast, when performing parallel analyses of the same samples using the BD Rhapsody platform, we recovered a much higher proportion of granulocyte gene transcripts, enabling true multi-modal characterization of human granulocyte heterogeneity.

immunology↗

bioRxiv2021

Aplp1 and the Aplp1-Lag3 Complex facilitates transmission of pathologic alpha-synuclein

Pathologic -synuclein (-syn) spreads from cell-to-cell, in part, through binding to the lymphocyte-activation gene 3 (Lag3). Here we report that amyloid {beta} precursor-like protein 1 (Aplp1) forms a complex with Lag3 that facilitates the binding, internalization, transmission, and toxicity of pathologic -syn. Deletion of both Aplp1 and Lag3 eliminates the loss of dopaminergic neurons and the accompanying behavioral deficits induced by -syn preformed fibrils (PFF). Anti-Lag3 prevents the internalization of -syn PFF by disrupting the interaction of Aplp1 and Lag3, and blocks the neurodegeneration induced by -syn PFF in vivo. The identification of Aplp1 and the interplay with Lag3 for -syn PFF induced pathology advances our understanding of the molecular mechanism of cell-to-cell transmission of pathologic -syn and provides additional targets for therapeutic strategies aimed at preventing neurodegeneration in Parkinsons disease and related -synucleinopathies. One Sentence SummaryAplp1 forms a complex with Lag3 that facilitates the binding, internalization, transmission, and toxicity of pathologic -synuclein. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=94 SRC="FIGDIR/small/442157v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@1d746bforg.highwire.dtl.DTLVardef@65acb2org.highwire.dtl.DTLVardef@12cf2f0org.highwire.dtl.DTLVardef@19d6e_HPS_FORMAT_FIGEXP M_FIG Aplp1 and the Aplp1-Lag3 complex facilitates transmission of pathologic -synuclein. Aplp1 is a receptor that drives pathologic -syn transmission, and genetic depletion of Aplp1 can significantly reduce the -synuclein pathogenesis. Aplp1 and Lag3 forms an Aplp1-Lag3 complex that accounts for substantial binding of pathologic -syn to cortical neurons. Together Aplp1 and Lag3 play a major role in pathologic -syn internalization, transmission and toxicity. Double knockout of Aplp1 and Lag3 and or a Lag3 antibody that disrupts the Aplp1 and Lag3 complex almost completely blocks -syn PFF-induced neurodegeneration. C_FIG

neuroscience↗

bioRxiv2020

Isolation and characterization of Streptomyces bacteriophages and Streptomyces strains encoding biosynthetic arsenals

The threat to public health posed by drug-resistant bacteria is rapidly increasing, as some of healthcares most potent antibiotics are becoming obsolete. Approximately two-thirds of the worlds antibiotics are derived from natural products produced by Streptomyces encoded biosynthetic gene clusters. Thus, in order to identify novel gene clusters, we sequenced the genomes of four bioactive Streptomyces strains isolated from the soil in San Diego County and used Bacterial Cytological Profiling adapted for agar plate culturing in order to examine the mechanisms of bacterial inhibition exhibited by these strains. In the four strains, we identified 101 biosynthetic gene clusters. Some of these clusters were predicted to produce previously studied antibiotics; however, the known mechanisms of these molecules could not fully account for the antibacterial activity exhibited by the strains, suggesting that novel clusters might encode antibiotics. When assessed for their ability to inhibit the growth of clinically isolated pathogens, three Streptomyces strains demonstrated activity against methicillin-resistant Staphylococcus aureus. Additionally, due to the utility of bacteriophages for genetically manipulating bacterial strains via transduction, we also isolated four new phages (BartholomewSD, IceWarrior, Shawty, and TrvxScott) against S. platensis. A genomic analysis of our phages revealed nearly 200 uncharacterized proteins, including a new site-specific serine integrase that could prove to be a useful genetic tool. Sequence analysis of the Streptomyces strains identified CRISPR-Cas systems and specific spacer sequences that allowed us to predict phage host ranges. Ultimately, this study identified Streptomyces strains with the potential to produce novel chemical matter as well as integrase-encoding phages that could potentially be used to manipulate these strains.

microbiology↗

bioRxiv2019

A novel totivirus alters gene expression and vacuolar morphology in Malassezia cells and induces a TLR3-mediated inflammatory immune response

Most fungal viruses have been identified in plant pathogens, whereas the presence of viral particles in human pathogenic fungi is less well studied. In the present study, we observed extrachromosomal double-stranded RNA (dsRNA) segments in various clinical isolates of Malassezia species. Malassezia is the most dominant fungal genus on the human skin surface, and species in this group are considered etiological factors of various skin diseases including dandruff, seborrheic dermatitis, and atopic dermatitis. We identified novel dsRNA segments, and our sequencing results revealed that the virus, named MrV40, belongs to the Totiviridae family and contains an additional satellite dsRNA segment encoding a novel protein. The transcriptome of virus-infected Malassezia restricta cells was compared to that of virus-cured cells, and the results showed that transcripts involved in ribosomal biosynthesis were downregulated and those involved in energy production and programmed cell death were upregulated. Moreover, transmission electron microscopy revealed significantly larger vacuoles in virus-infected M. restricta cells, indicating that MrV40 infection dramatically altered M. restricta physiology. Our analysis also revealed that viral nucleic acid from MrV40 induced a TLR3-mediated inflammatory immune response in bone marrow-derived dendritic cells, suggesting that a viral element contributes to the pathogenicity of Malassezia. ImportanceMalassezia is the most dominant fungal genus on the human skin surface and is associated with various skin diseases including dandruff and seborrheic dermatitis. Among Malassezia species, Malassezia restricta is the most widely observed species on the human skin. In the current study, we identified a novel dsRNA virus, named MrV40, in M. restricta and characterized the sequence and structure of the viral genome along with an independent satellite dsRNA viral segment. Moreover, expression of genes involved in ribosomal synthesis and programmed cell death was altered, indicating that virus infection affected the physiology of the fungal host cells. Our data also showed that the viral nucleic acid from MrV40 induces a TLR3-mediated inflammatory immune response in bone marrow-derived dendritic cells, indicating that a viral element likely contributes to the pathogenicity of Malassezia. This is the first study to identify and characterize a novel mycovirus in Malassezia.

microbiology↗

bioRxiv2019

Stable isotope composition of feathers help track the migratory patterns of Sharp-shinned Hawks (Accipiter striatus) along Western Flyways of North America

The large-scale patterns of movement for the Sharp-shinned Hawk (Accipiter striatus), a small forest hawk found throughout western North America, are largely unknown. However, based on field observations we set out to test the hypothesis that juvenile migratory A. striatus caught along two distinct migration routes on opposite sides of the Sierra Nevada Mountains of North America (Pacific Coast and Intermountain Migratory Flyways) come from geographically different natal populations. We applied stable isotope analysis of hydrogen (H) and oxygen (O) of feathers, and large scale models of spatial isotopic variation (isoscapes) to formulate spatially explicit predictions of the origin of the migrant birds. Novel relationships were assessed between the measured hydrogen and oxygen isotope values of feathers from A. striatus museum specimens of known origin and the isoscape modeled hydrogen and oxygen isotope values of precipitation at those known locations. We used these relationships to predict the origin regions for birds migrating along the two flyways from the measured isotope values of migrants feathers and the associated hydrogen and oxygen isotopic composition of precipitation where these feathers were formed. The birds from the two migration routes had overlap in their natal/breeding origins and did not differentiate into fully separate migratory populations, with birds from the Pacific Coast Migratory Flyway showing broader natal geographic origins then those from the Intermountain Flyway. The methodology based on oxygen isotopes had, in general, less predictive power than the one based on hydrogen. There was broad agreement between the two isotope approaches in the geographic assignment of the origins of birds migrating along the Pacific Coast Flyway, but not for those migrating along the Intermountain Migratory Flyway. These results are discussed in terms of their implications for conservation efforts of A. striatus in western North America, and the use of combined hydrogen and oxygen stable isotope analysis to track the movement of birds of prey on continental scales.

zoology↗

bioRxiv2019

Genetic modifiers of risk and age at onset in GBA associated Parkinson disease and Lewy body dementia

Parkinsons disease (PD) is a genetically complex disorder. Multiple genes have been shown to contribute to the risk of PD, and currently 90 independent risk variants have been identified by genome-wide association studies. Thus far, a number of genes (including SNCA, LRRK2, and GBA) have been shown to contain variability across a spectrum of frequency and effect, from rare, highly penetrant variants to common risk alleles with small effect sizes. Variants in GBA, encoding the enzyme glucocerebrosidase, are associated with Lewy body diseases such as PD and Lewy body dementia (LBD). These variants, which reduce or abolish enzymatic activity, confer a spectrum of disease risk, from 1.4- to >10-fold. An outstanding question in the field is what other genetic factors that influence GBA-associated risk for disease, and whether these overlap with known PD risk variants.\n\nUsing multiple, large case-control datasets, totalling 217,165 individuals (22,757 PD cases, 13,431 PD proxy cases, 622 LBD cases and 180,355 controls), we identified 1,772 PD cases, 711 proxy cases and 7,624 controls with a GBA variant (p.E326K, p.T369M or p.N370S). We performed a genome-wide association study and analysed the most recent PD-associated genetic risk score to detect genetic influences on GBA risk and age at onset. We attempted to replicate our findings in two independent datasets, including the personal genetics company 23andMe, Inc. and whole-genome sequencing data. Our analysis showed that the overall PD genetic risk score modifies risk for disease and decreases age at onset in carriers of GBA variants. Notably, this effect was consistent across all tested GBA risk variants. Dissecting this signal demonstrated that variants in close proximity to SNCA and CTSB (encoding cathepsin B) are the most significant contributors. Risk variants in the CTSB locus were identified to decrease mRNA expression of CTSB. Additional analyses suggest a possible genetic interaction between GBA and CTSB and GBA p.N370S neurons were shown to have decreased Cathepsin B expression compared to controls. These data provide a genetic basis for modification of GBA-associated PD risk and age at onset and demonstrate that variability at genes implicated in lysosomal function exerts the largest effect on GBA associated risk for disease. Further, these results have important implications for selection of GBA carriers for therapeutic interventions.

genetics↗

bioRxiv2019

Functional dissection of Alzheimer’s disease brain gene expression signatures in humans and mouse models

Human brain transcriptomes can highlight biological pathways associated with Alzheimers disease (AD); however, challenges remain to link expression changes with causal triggers. We have examined 30 AD-associated, gene coexpression modules from human brains for overlap with 251 differentially-expressed gene sets from mouse brain RNA-sequencing experiments, including from models of AD and other neurodegenerative disorders. Human-mouse overlaps highlight responses to amyloid versus neurofibrillary tangle pathology and further reveal age- and sex-dependent expression signatures for AD progression. Human coexpression modules enriched for neuronal and/or microglial genes overlap broadly with signatures from mouse models of AD, Huntingtons disease, Amyotrophic Lateral Sclerosis, and also aging. Several human AD coexpression modules, including those implicated in the unfolded protein response and oxidative phosphorylation, were not activated in AD models, but instead were detected following other, unexpected mouse genetic manipulations. Our results comprise a powerful, cross-species resource and pinpoint experimental models for diverse features of AD pathophysiology from human brain transcriptomes.

systems biology↗

bioRxiv2018

Heritability and genetic variance of dementia with Lewy bodies

Recent large-scale genetic studies have allowed for the first glimpse of the effects of common genetic variability in dementia with Lewy bodies (DLB), identifying risk variants with appreciable effect sizes. However, it is currently well established that a substantial portion of the genetic heritable component of complex traits is not captured by genome-wide significant SNPs. To overcome this issue, we have estimated the proportion of phenotypic variance explained by genetic variability (SNP heritability) in DLB using a method that is unbiased by allele frequency or linkage disequilibrium properties of the underlying variants. This shows that the heritability of DLB is nearly twice as high as previous estimates based on common variants only (31% vs 59.9%). We also determine the amount of phenotypic variance in DLB that can be explained by recent polygenic risk scores from either Parkinsons disease (PD) or Alzheimers disease (AD), and show that, despite being highly significant, they explain a low amount of variance. Additionally, to identify pleiotropic events that might improve our understanding of the disease, we performed genetic correlation analyses of DLB with over 200 diseases and biomedically relevant traits. Our data shows that DLB has a positive correlation with education phenotypes, which is opposite to what occurs in AD. Overall, our data suggests that novel genetic risk factors for DLB should be identified by larger GWAS and these are likely to be independent from known AD and PD risk variants.

neuroscience↗