Edward B. Lee

Exploring transcriptomic and genomic latent variable correction approaches in differential expression analysis.

This paper evaluates combining expression-based surrogate variables and genotype-based principal components in differential expression analysis, finding the combined approach improves replicability and biological recall in ALS datasets.

Large-scale cerebrospinal fluid proteomics identifies diagnostic biomarker candidates across the clinico-pathological continuum of frontotemporal lobar degeneration

The paper identifies potential diagnostic biomarkers for frontotemporal lobar degeneration subtypes using cerebrospinal fluid proteomics.

Structural heterogeneity of CTE Type I tau filaments with an interface-shifted polymorph

The paper analyzes cryo-EM data of CTE tau filaments, identifying a new CTE Type I-like structure with a shifted protofilament interface and showing its coexistence with the canonical CTE Type I structure within fibrils.

Repositioning of polyubiquitin alters the pathologic tau filament structure

This study shows that polyubiquitin repositioning affects tau filament structure in tauopathies, altering their seeding activity in mice.

Postmortem brain MRI reveals differential associations of subcortical and limbic volumes with cortical thinning and neurodegenerative pathologies

The paper examines subcortical and limbic volume associations with cortical thinning and neurodegenerative pathologies in postmortem brain MRI data from multiple disease groups.

Single-Nuclei Transcriptomic Characterization of APOE4-Associated Alzheimer's Disease

This study characterizes cell-type-specific transcriptomes across APOE genotypes in Alzheimer's disease using single-nuclei RNA sequencing, revealing APOE4-associated changes in excitatory neurons and microglia.

Microglial reactivity in the hippocampal CA2 is associated with advanced neuronal α-synucleinopathy

This study examines the association between microglial reactivity and neuronal α-synucleinopathy in specific hippocampal subfields in Lewy body disease patients.

Network-based amyloid-beta pathology predicts subsequent cognitive decline in cognitively normal older adults

This study uses machine learning to show that integrating brain connectome data with amyloid-beta PET imaging improves prediction of cognitive decline in older adults.

Characterization of hippocampal subfields using histology-based annotated postmortem MRI: Lessons for in vivo segmentation II

The paper characterizes hippocampal subfield border variability using postmortem MRI and histology, finding consistent subfield appearance/disappearance orders and no clear diagnosis-related differences.

Super-Resolution Imaging Uncovers Nanoscale Tau Aggregate Hyperphosphorylation Patterns in Human Alzheimers Disease Brain Tissue

The paper uses super-resolution imaging to analyze nanoscale tau aggregates in AD and PART brain tissues, revealing hyperphosphorylation patterns and morphological differences.

Accumulation of LRRK2-associated phospho-Rab12 degenerative lysosomes in tauopathies

This study shows that LRRK2-mediated phosphorylation of Rab12 accumulates in lysosomal-like structures in tauopathies and synucleinopathies, linking LRRK2 kinase activity to endolysosomal dysfunction.

Hemispheric Asymmetry of Tau Pathology is Related to Asymmetric Amyloid Deposition in Alzheimer's Disease

The paper investigates whether hemispheric asymmetry in tau pathology in Alzheimer's disease is linked to reduced inter-hemispheric connectivity or asymmetric amyloid-beta distribution, finding a strong association with amyloid-beta laterality.

Tau Aggregation Results in an Impaired Ability to Counteract Microtubule Destabilization via Specific Combinatorial Tau Phosphorylation Patterns

This study shows that tau phosphorylation patterns influence microtubule stability, with specific phosphorylations impairing tau's ability to counteract destabilization, suggesting phosphorylation may respond to, rather than precede, MT instability.

Developing an anatomically valid segmentation protocol for anterior regions of the medial temporal lobe for neurodegenerative diseases

The paper develops a segmentation protocol for anterior medial temporal lobe regions and integrates it into an automated approach to improve imaging biomarkers for neurodegenerative diseases.

Parkinson's disease-vulnerable and -resilient dopamine neurons display opposite responses to excitatory input

The paper identifies Anxa1 as a marker for PD-vulnerable dopamine neurons and shows they respond oppositely to excitatory inputs compared to resilient Vglut2+ neurons.

Deciphering Distinct Genetic Risk Factors for FTLD-TDP Pathological Subtypes via Whole-Genome Sequencing

This study identifies genetic risk factors for FTLD-TDP subtypes using whole-genome sequencing and meta-analysis across multiple cohorts.

Context-dependent Interactors Regulate TDP-43 Dysfunction in ALS/FTLD

The paper identifies context-dependent interactors of TDP-43 that regulate its dysfunction in ALS/FTLD using proximity labeling, mass spectrometry, and snRNA-seq integration.

Hyperactive neuronal networks enhance tau spread in an Alzheimer's disease mouse model

This study shows that neuronal hyperactivity and seizures increase tau spread in an Alzheimer's disease mouse model and correlate with memory deficits.

Large- Scale Deep Proteomic Analysis in Alzheimer's Disease Brain Regions Across Race and Ethnicity

The paper performs large-scale proteomic analysis of Alzheimer's disease brain regions across different racial and ethnic groups, identifying AD-related protein changes and APOE4 concordance with genotype.

Bridging the Gap: Multi-Omics Profiling of Brain Tissue in Alzheimer's Disease and Older Controls in Multi-Ethnic Populations

This paper presents a multi-omics dataset from multi-ethnic Alzheimer's disease brain donors, including transcriptome, genome, and proteome data, to improve precision medicine for underrepresented populations.

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.

Cytoarchitectonic gradients of laminar degeneration in behavioral variant frontotemporal dementia

This study examines laminar neurodegeneration patterns in bvFTD-tau and bvFTD-TDP, finding progressive SMI32-ir loss along a frontal cortical gradient in tau pathology.

Network Proteomics of the Lewy Body Dementia Brain Reveals Presynaptic Signatures Distinct from Alzheimer's Disease

This study identifies distinct presynaptic protein networks in Lewy body dementia that differ from Alzheimer's disease using network proteomics.

α-Synuclein Conformations in Plasma Distinguish Parkinson's Disease from Dementia with Lewy Bodies

The paper identifies plasma α-synuclein conformations that distinguish Parkinson's disease from dementia with Lewy bodies and predict cognitive decline in PD.

Human iPSC 4R tauopathy model uncovers modifiers of tau propagation

The paper creates a human iPSC model of 4R tauopathy and identifies genetic modifiers of Tau propagation using CRISPRi screening.

Deep sequencing of proteotoxicity modifier genes uncovers a Presenilin-2/beta-amyloid-actin genetic risk module shared among alpha-synucleinopathies

The paper identifies a shared genetic risk module involving PSEN2 and actin regulation across alpha-synucleinopathies, linking them to Alzheimer's disease mechanisms.

Comparison of histological delineations of medial temporal lobe cortices by four independent neuroanatomy laboratories

This paper compares cytoarchitectonic delineations of medial temporal lobe subregions by four neuroanatomists, finding higher agreement in some areas and less in others.

Multi-omics Characterization of Epigenetic and Genetic Risk of Alzheimer Disease in Autopsied Brains from two Ethnic Groups

The paper identifies six genetic loci associated with Alzheimer's disease in Hispanics, showing both genetic and epigenetic risks, with some downstream effects on mRNA expression being ethnicity-specific.

Disease-specific selective vulnerability and neuroimmune pathways in dementia revealed by single cellgenomics

The paper uses single-cell genomics to identify shared and disease-specific cell states and gene regulatory networks in three dementias, revealing distinct neuroimmune mechanisms and potential therapeutic targets.

A Novel Autosomal Dominant Childhood-Onset Disorder Associated with Pathogenic Variants in VCP

The paper identifies novel VCP variants causing a childhood-onset neurodevelopmental disorder through exome sequencing and functional analysis.