David Klenerman

This paper introduces a new spectral single-molecule microscopy technique using spatially patterned detectors, achieving spectral and positional resolution without complex optical components.

This study uses SiMPull to detect nanoscopic tau aggregates in PD brain regions, finding high-intensity aggregates in some PD cases despite negative IHC results.

The paper shows TNFα promotes tau aggregation at pre-synapses in human neurons, forming non-fibrillar aggregates that replicate rapidly.

This paper provides a protocol for building and characterizing an oblique plane microscope (OPM) to enable fast, multi-color, high-resolution volumetric fluorescence imaging with reduced phototoxicity.

The paper identifies disease-specific molecular profiles of small tau aggregates across different tauopathies using single-molecule assays.

The paper examines tau aggregates in Alzheimer's disease synaptosomes, finding that small tau aggregates are associated with early synaptic pathology.

This paper introduces patch deconvolution to accelerate 3D cellular imaging in Fourier light-field microscopy, achieving faster reconstruction speeds without compromising quality.

This study shows that hyaluronidase improves CEACAM5 accessibility on colorectal cancer cells, enhancing CAR T-cell therapy effectiveness by reducing glycocalyx thickness and restoring sustained T-cell activation.

The paper tracks SOX2 and NANOG dynamics in live cells using advanced microscopy and analysis pipelines, revealing differences in their spatiotemporal behavior due to protein-protein interactions.

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.

The paper uses super-resolution microscopy and SIMOA to analyze alpha-synuclein aggregates in Parkinson's disease brain samples and mouse models, finding larger aggregates in PD samples and differences based on extraction methods.

The paper identifies a cellular tipping point between aggregate accumulation and removal as a universal feature of neurodegeneration, validated through live-cell assays and super-resolution imaging.

The paper shows that T-cell activation is initiated by partial CD45 exclusion at sub-micron contacts, leading to strong activation and cytotoxicity through small signaling changes.

This paper introduces a combined SICM-OPM system for simultaneous non-contact topographical and volumetric fluorescence imaging in live cells, demonstrating its use in studying cellular remodeling and molecular delivery.

This study shows human astrocytes generate and release amyloid-β aggregates under lysosomal stress, contributing to extracellular Aβ accumulation in Alzheimer's disease.

The paper shows that astrocytic RNA editing via ADAR1 modulates immune responses to alpha-synuclein, contributing to neuroinflammation in Parkinson's disease.

This study uses single molecule microscopy to fingerprint TDP-43 aggregates in brain tissue, distinguishing MND donors from controls and different MND cohorts.

This study shows MLL2 stabilizes 3D chromatin loops during pluripotent cell differentiation without requiring its enzymatic activity.

The paper quantifies proteasome re-organization during proteotoxic stress using single-molecule microscopy and shows cytoskeleton-dependent movement restrictions.

The paper uses single-molecule detection and super-resolution imaging to analyze how four monoclonal antibodies bind to beta-amyloid aggregates, finding Lecanemab has superior binding properties.

This study shows that downregulating FBXO2 in human iPSC-derived neurons leads to Alzheimer's disease-like features including Aβ aggregation and tau hyperphosphorylation.

SynPull combines single-molecule pulldown, super-resolution microscopy, and computational analysis to study protein aggregates in synaptosomes from human and mouse samples, revealing AT8-positive tau as the predominant aggregate in Alzheimer's disease.

This study shows that oligodendrocytes produce amyloid beta in Alzheimer's Disease and that suppressing this production improves brain pathology and neuronal function.

The paper shows that apoE isoforms modulate Aβ aggregation, clearance, and toxicity in Alzheimer's disease, with implications for therapeutic strategies.

The paper investigates the formation of amyloid loops in brain tissues and finds that protofibril flexibility, not hydrogen bonding, enables loop formation and disease-related toxicity.

The paper tracks α-synuclein conformational changes in neurons and shows mitochondrial involvement in oligomerization and toxicity.

This study shows that CSP reduces synuclein aggregates and restores dopamine release in a Parkinson's disease mouse model.

The paper examines soluble Aβ aggregates in CSF from AD, MCI, and healthy controls, finding stage-specific differences in aggregate size and toxicity mechanisms.