Bradley T. Hyman

The paper uses subcellular spatial transcriptomics to identify why some neurons in Alzheimer's disease accumulate tau while others resist it, finding differences in molecular programs and neuron-glia interactions.

The paper introduces multiDIA, a proteomics method that improves sequence coverage and scalability in neurodegenerative disease studies by combining multiple proteases and data-independent acquisition.

This study identifies tRNA-derived fragments (tRFs) as key regulators of Tau aggregation in Alzheimer's disease and shows their potential as therapeutic targets.

This study identifies Arc as critical for packaging tau into extracellular vesicles, facilitating its release and intercellular transmission in Alzheimer's disease.

The paper uses single-nucleus RNA-seq to analyze cerebrovascular transcriptomic changes in Alzheimer's Disease and primary tauopathies, identifying shared heat-shock responses and disease-specific vascular remodeling.

The paper develops BiTSA, a bioluminescence-based thermal stability assay, to characterize isoform-dependent thermal stability of ApoE variants in living cells and confirms that ApoE4 is less stable than ApoE3 in native tissue.

This study investigates whether distinct α-synuclein strains contribute to clinical subtypes of multiple system atrophy (MSA) and finds no differences in strain properties between MSA-C and MSA-P.

The paper shows that O-glycans in LRP1's ligand-binding domains differentially modulate uptake of tau and amyloid beta, but not RAP or ApoE.

The paper shows lipidated ApoE is closely located to Aβ aggregates in human Alzheimer's brains, suggesting a role in plaque formation.

This study shows amyloid plaques in the hippocampus cause long-range circuit reorganization in freely behaving mice, affecting place cell distribution and functional maps.

This study identifies dynamic conformational states of soluble Tau that precede aggregation and correlate with neuronal toxicity in Alzheimer's disease and related tauopathies.

The paper shows UV exposure causes misfolded melanosomal proteins to aggregate, contributing to skin pigmentation disorders and melanocyte dysfunction.

This study compares four methods of purifying α-synuclein for seed amplification assays, finding that osmotic shock-purified monomer has the lowest aggregation propensity and best inter-batch reproducibility.

This study shows that tau seeding in neurons occurs via transient endolysosomal perforations that remain confined within endolysosomes and require PIKfyve activity.

This study presents a single-cell multi-omic atlas of Alzheimer's disease brain regions, revealing region-specific epigenomic changes and altered cell states.

The paper identifies rare bioactive tau oligomers in Alzheimer's brain that can induce templated misfolding and fibril formation, distinguishing them from non-bioactive oligomers.

This paper uses micro-XRD and XRF to analyze tau aggregates in Pick's disease, finding distinct elemental compositions and fibril structures in different lesion types.

This study shows that tau accumulation leads to neuronal silencing and network dysfunction in the hippocampal formation without neuron loss, contributing to progressive network disruption.

This study identifies proteomic changes in Alzheimer's disease, revealing decreased 20S proteasome levels and altered ubiquitin system enzymes contributing to protein accumulation.

The paper examines somatic mutations in neurons across tau pathologic states in Alzheimer's disease and finds increased mutation burden and specific mutational signatures in AD neurons.

The paper uses snRNA-seq and spatial transcriptomics to study oligodendroglia in Parkinson's disease, identifying disease-specific subclasses and transcriptomic changes linked to myelin integrity and cell communication.

This study identifies big tau, a splice isoform of tau, as more abundant in brain regions resistant to Alzheimer's pathology and shows its protective properties in human patients.

The paper uses snRNA-seq to identify eight interneuron classes in the human dorsal striatum, validates markers with in situ hybridization, and compares them to mouse interneurons.

The paper shows tau accumulates around blood vessels in Alzheimer's disease brains and is linked to tau tangle pathology.

This paper shows that APOE2 gene therapy reduces amyloid deposition, neurodegeneration, and microglial activation in an Alzheimer's mouse model with ongoing APOE4 expression.

The paper develops open-source tools for 3D analysis of brain dissection photographs and surface scans, achieving accurate reconstructions and segmentations comparable to MRI.

The paper examines transcriptomic changes in Alzheimer's disease brain regions associated with Aβ plaques, tangles, and APOE ε4, finding distinct gene expression patterns linked to neuroinflammation and neuronal dysfunction.

The paper compares the bioactivity of fibrillar and oligomeric tau forms in Alzheimer's disease, finding HMW tau more potent in glial activation and tau propagation.

The paper analyzes endothelial cell heterogeneity across brain regions in Alzheimer's disease using single nucleus RNAseq, revealing region-specific gene expression changes and disease-related transcriptomic alterations.

This study identifies truncated Aβ fragments that form SDS-stable, low molecular weight oligomers impairing synaptic plasticity and evading conventional antibodies.