Alison Goate

Comprehensive adjudication identifies 111 high-confidence loci for Alzheimer's disease and related dementias

The paper systematically adjudicates genetic evidence for Alzheimer's disease and related dementias, identifying 111 high-confidence loci through a tiered framework applied to large-scale genome-wide studies.

A rapid, genetically-tractable human iPSC-derived model for studying tissue-resident macrophage biology in Alzheimer's and other diseases

This paper develops a simplified protocol to generate human iPSC-derived macrophage-like cells (iMacs) that exhibit enhanced phagocytic and TREM2-related functions, making them a useful model for studying macrophage biology in Alzheimer's and other diseases.

LRRK2 G2019S variant is associated with transcriptional changes in Parkinson's disease human myeloid cells under proinflammatory environment

This study shows the G2019S LRRK2 mutation alters transcriptomes of myeloid cells under proinflammatory conditions, affecting lipid metabolism and phagocytic function.

Distribution of big tau isoforms in the human central and peripheral nervous system

The paper characterizes big tau isoforms in human nervous system tissues and CSF, finding they are enriched in the peripheral nervous system and largely unaffected by neurodegenerative disease.

Genetic Associations with Temporal Modeling of Alzheimer's Disease Progression Supports a Novel Paradigm for Disease Risk

This paper uses temporal modeling of Alzheimer's disease progression with metabolomics data to identify novel genetic loci associated with disease speed, independent of traditional case-control associations.

A TAD-informed aging-brain xQTL atlas of multi-modal and cell-type-resolved regulatory variation

The paper presents an xQTL atlas of regulatory variation in the aging human brain, integrating multiple modalities and cell types across four studies, identifying more variant-molecular-trait associations by including TAD boundaries.

Multiomic Profiling of 85 iPSC Lines from Familial Dementia Reveals Cellular Diversity and Regulators of Organoid Development

The paper characterizes 85 MAPT mutation-bearing iPSC lines using multiomic approaches, revealing cellular diversity and factors influencing organoid development.

Reduced LACTB expression in myeloid cells is associated with elevated succinylcarnitine levels and reduced Alzheimers disease risk.

The paper investigates the role of LACTB in Alzheimer's disease risk through Mendelian Randomization and experimental models, finding reduced LACTB expression lowers AD risk and increases succinylcarnitine levels.

Early microglial priming in Alzheimer's disease revealed by ME-seq

The paper introduces ME-seq, a technology that profiles DNA methylation, gene expression, and chromatin accessibility in single nuclei, revealing early microglial priming in Alzheimer's disease.

Evaluating the causal effect of mitochondrial dysfunction on Alzheimer's and Parkinson's disease using Polygenic Risk Scores and Mendelian Randomization

This paper uses Polygenic Risk Scores and Mendelian Randomization to evaluate the causal effect of mitochondrial DNA copy number on Alzheimer's and Parkinson's disease risk.

Alternative Anastrozole Target CYP4V2 Impairs Neurons in Preclinical Models of Inherited Tauopathy

This study identifies anastrozole's off-target CYP4V2 as a neuroprotective factor in tauopathy models by reducing Tau phosphorylation and oxidative stress.

APOE4 promotes cerebrovascular fibrosis and amyloid deposition via a pericyte-to-myofibroblast transition

This study identifies APOE4-driven pericyte-to-myofibroblast transition in cerebrovascular disease, leading to fibrosis and amyloid deposition, and shows TGF-β inhibition can reverse these effects.

Cytokine-induced reprogramming of human macrophages toward Alzheimer's disease-relevant molecular and cellular phenotypes in vitro

This study reprograms human macrophages in vitro using cytokines to mimic Alzheimer's disease-relevant phenotypes, showing transcriptomic and functional changes similar to disease-associated microglia.

High-throughput measurements of neuronal activity in single human iPSC-derived glutamate neurons

This paper develops a high-throughput method to measure neuronal activity in human iPSC-derived glutamatergic neurons using Mg2+-free ACSF and confirms donor-specific firing patterns.

Long-read RNA-seq atlas of novel microglia isoforms elucidates disease-associated genetic regulation of splicing

The paper presents a long-read RNA-seq atlas of microglia isoforms, identifying novel isoforms and their associations with genetic risk loci in Alzheimer's and Parkinson's disease.

Integrative genomics approach identifies glial transcriptomic dysregulation and risk in the cortex of individuals with Alcohol Use Disorder

The paper identifies glial transcriptomic dysregulation and genetic risk in the cortex of individuals with Alcohol Use Disorder using single nuclei RNA-sequencing.

APOE and TREM2 variants differentially influence glial fibrillary acidic protein and neurofilament light in plasma of UK Biobank participants

This study examines how APOE and TREM2 variants influence plasma levels of GFAP and NEFL in UK Biobank participants, finding age-dependent effects and associations with dementia risk.

Divergent Effects of APOE3 and APOE4 Human Astrocytes on Key Alzheimer's Disease Hallmarks in Chimeric Mice

This study shows that APOE3 and APOE4 human astrocytes differentially affect Alzheimer's disease hallmarks in chimeric mice, with APOE3 reducing and APOE4 worsening pathology.

Genetic, transcriptomic, histological, and biochemical analysis of progressive supranuclear palsy implicates glial activation and novel risk genes

This study identifies six genetic loci associated with progressive supranuclear palsy, including a novel locus, and links them to oligodendrocytic dysfunction and C4A expression.

Missense and Loss of Function Variants at GWAS Loci in Familial Alzheimer's Disease

The paper examines rare missense and loss of function variants in GWAS loci for Alzheimer's disease across families, finding that many families lack identifiable variants beyond APOE-e4.

Whole-Genome Sequencing Analysis Reveals New Susceptibility Loci and Structural Variants Associated with Progressive Supranuclear Palsy

This study uses whole-genome sequencing to identify new genetic loci and structural variants associated with progressive supranuclear palsy, including novel signals in APOE and H1/H2 haplotype region variants.

Integrated Single-Cell Multiomic Profiling of Caudate Nucleus Suggests Key Mechanisms in Alcohol Use Disorder

The paper uses multiomic profiling of the caudate nucleus to identify gene expression and chromatin changes in AUD, linking them to risk genes through QTL analysis.

Upregulated GIRK2 counteracts ethanol-induced changes in excitability and respiration in human neurons

The paper investigates how upregulated GIRK2 affects ethanol-induced changes in human neurons, showing it counteracts excitability and respiration changes.

Proteo-genomics of soluble TREM2 in cerebrospinal fluid provides novel insights and identifies novel modulators for Alzheimer disease

This study identifies four novel genetic loci associated with soluble TREM2 levels in CSF through GWAS and provides functional validation of their roles in Alzheimer's disease.

Integrated Manufacturing Platform for Cortical Organoids Reveals Early Phosphatase and Prefoldin Dysregulation in MAPT V337M Neurons

The paper develops a scalable cortical organoid platform with quality control metrics and identifies early dysregulation of phosphatase and prefoldin genes in FTD-tau neurons.

Development of MAPT S305 mutation models exhibiting elevated 4R tau expression, resulting in altered neuronal and astrocytic function

This study develops isogenic iPSC lines with MAPT S305 mutations to increase 4R tau expression, revealing altered neuronal and astrocytic functions in tauopathies.

Genetic influences vary by age and sex: Trajectories of the association of cholinergic system variants and theta band event related oscillations

The paper examines how genetic variants in the cholinergic system affect theta band event-related oscillations, finding age and sex-dependent variations in these associations.

BHLHE40/41 regulate macrophage/microglia responses associated with Alzheimer's disease and other disorders of lipid-rich tissues

This study identifies BHLHE40/41 as key regulators of macrophage/microglia responses in Alzheimer's disease and other lipid-rich tissue disorders through sc/nRNA-seq analysis and functional validation.

The Role of Mitochondrial genome abundance in Alzheimer's Disease

The paper investigates the association between mitochondrial genome abundance and Alzheimer's disease, finding lower abundance correlates with worse neuropathology and cognitive performance.

Alcohol reverses the effects of KCNJ6 (GIRK2) noncoding variants on excitability of human glutamatergic neurons

This study shows that KCNJ6 noncoding variants increase excitability in human glutamatergic neurons, an effect reversed by ethanol exposure.