John Q. Trojanowski

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.

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.

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.

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.

Glucocerebrosidase activity and lipid levels are related to protein pathologies in Parkinson's disease

The paper examines the relationship between glucocerebrosidase activity, lipid levels, and protein pathologies in Parkinson's disease and dementia with Lewy bodies.

Genome-wide association study of autopsy-confirmed Multiple System Atrophy identifies common variants near ZIC1 and ZIC4

Tau interactome mapping reveals dynamic processes in synapses and mitochondria associated with neurodegenerative disease

The paper maps Tau interactomes in neurons using APEX and AP-MS to reveal activity-dependent interactions and FTD mutation effects on mitochondrial associations in neurodegenerative diseases.

Single-nuclei isoform RNA sequencing reveals combination patterns of transcript elements across human brain cell types

The paper introduces SnISOr-Seq, a method for single-nuclei isoform RNA sequencing, and finds distinct combination patterns of transcript elements in human brain cell types.

Genome-wide association study and functional validation implicates JADE1 in tauopathy

This study identifies JADE1 as a novel genetic factor in tauopathy through genome-wide association and functional validation in human and Drosophila models.

TMEM106B modifies TDP-43 pathology in human ALS brain and cell-based models of TDP-43 proteinopathy

This study investigates how TMEM106B and C9orf72 genetic variants influence TDP-43 pathology in ALS and FTLD-TDP, finding TMEM106B modifies TDP-43 aggregation severity.

Tau pathology spreads between anatomically-connected regions of the brain and is modulated by a LRRK2 mutation

This study shows tau pathology spreads along anatomical brain connections and a LRRK2 mutation alters its directionality in mice.

Genome-wide association studies of LRRK2 modifiers of Parkinson's disease

This study identifies genetic modifiers of LRRK2 mutations in Parkinson's disease, finding a significant variant in CORO1C and a polygenic risk score effect on penetrance.

Joint ex vivo MRI and histology detect iron-rich cortical gliosis in Tau and TDP-43 proteinopathies

This study uses joint ex vivo MRI and histology to identify distinct iron-rich gliosis patterns in FTLD-Tau and FTLD-TDP, distinguishing them from other neurodegenerative conditions.

3D Mapping of Neurofibrillary Tangle Burden in the Human Medial Temporal Lobe

This study creates 3D maps of neurofibrillary tangle burden in the human medial temporal lobe using ex vivo MRI and dense histology, revealing variation along the anterior-posterior axis and widespread NFT distribution.

Tracking tau fibrillogenesis and consequent primary phagocytosis of neurons mediated by microglia in a living tauopathy model

This study tracks tau fibrillogenesis and microglial phagocytosis of neurons in a living tauopathy model, showing that microglia engulf tangle-bearing neurons and that TSPO ligands can reduce this process.

Defining and predicting transdiagnostic categories of neurodegenerative disease

This paper defines transdiagnostic disease categories using histopathological data and predicts cluster membership from CSF and genotype data with high accuracy.

Synapsin-caveolin-1 mitigates cognitive deficits and neurodegeneration in Alzheimer's disease mice

This study shows that re-expressing caveolin-1 in Alzheimer's disease mice improves cognitive function and reduces neurodegeneration without affecting amyloid deposits.

Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into the complex genetic architecture

This paper identifies five new genetic risk loci for Lewy body dementia through whole-genome sequencing and shows shared risk profiles with Alzheimer’s and Parkinson’s disease.

The Sigma-2 Receptor/TMEM97, PGRMC1, and LDL Receptor complex are responsible for the cellular uptake of Aβ42 and its protein aggregates

This study identifies the Sigma-2 receptor/TMEM97, PGRMC1, and LDLR complex as a pathway for Aβ42 uptake in neurons, both with and without apoE, suggesting it as a potential therapeutic target for Alzheimer's disease.

ATN status in amnestic and non-amnestic Alzheimer's disease and frontotemporal lobar degeneration

This paper evaluates the ATN framework's accuracy in diagnosing Alzheimer's disease subtypes and frontotemporal lobar degeneration using cerebrospinal fluid biomarkers, finding that non-amnestic Alzheimer's patients have lower tau levels and the framework is less sensitive to frontotemporal lobar degeneration.

A Consensus Proteomic Analysis of Alzheimer's Disease Brain and Cerebrospinal Fluid Reveals Early Changes in Energy Metabolism Associated with Microglia and Astrocyte Activation

The paper identifies protein network modules in Alzheimer's disease brains and cerebrospinal fluid that are associated with energy metabolism and neuroinflammation, suggesting potential biomarkers and therapeutic targets.

Poly(ADP-ribose) induces α-synuclein aggregation in neuronal-like cells andinteracts with phosphorylated α-synuclein in post mortem PD samples

This study shows that PAR promotes α-synuclein aggregation and interacts with phosphorylated α-synuclein in Parkinson's disease samples.

The Alzheimer’s Disease Metabolome: Effects of Sex and APOE ε4 genotype

The paper investigates sex and APOE ε4 genotype effects on metabolic alterations in Alzheimer’s disease using stratified analysis of serum metabolites.

Serum triglycerides in Alzheimer’s disease: Relation to neuroimaging and CSF biomarkers

The paper investigates the association between triglyceride principal component scores and Alzheimer's disease biomarkers in the ADNI cohort, finding significant links with MCI, AD, and specific brain structures.

Heritability and genetic variance of dementia with Lewy bodies

This study estimates the heritability of dementia with Lewy bodies (DLB) and finds it to be higher than previous estimates, with low variance explained by polygenic risk scores from Parkinson's or Alzheimer's disease.

Altered Bile Acid Profile Associates with Cognitive Impairment in Alzheimer’s Disease – An Emerging Role for Gut Microbiome

The paper identifies altered bile acid profiles in Alzheimer's disease, linking them to cognitive impairment and genetic variants through a large study.

Altered Bile Acid Profile in Mild Cognitive Impairment and Alzheimer’s Disease: Relationship to Neuroimaging and CSF Biomarkers

The paper identifies associations between serum bile acid metabolites and AD biomarkers in the A/T/N framework, suggesting a potential role for bile acid pathways in AD pathophysiology.

A comprehensive assessment of benign genetic variability for neurodegenerative disorders

The paper assesses benign genetic variability in elderly individuals without neurodegenerative disease to aid in distinguishing pathogenic mutations.