J. Nicholas Cochran

AlphaGenome identifies a deep intronic variant in a family with PLA2G6-associated neurodegeneration: Closing the diagnostic gap in rare genetic diseases

Integrative Genomic and Functional Analyses Reveal NINL as a Modulator of Tau Aggregation

The paper identifies NINL as a modulator of tau aggregation through integrative genomic and functional analyses linking it to proteostasis dysfunction in FTD and AD.

Promoter mutagenesis and a massively parallel reporter screen of the MAPT locus identifies cis-regulatory elements and genetic variation effects

The paper identifies cis-regulatory elements and genetic variation effects in the MAPT locus using MPRA and CRISPRi in neuronal and HEK293FT cells.

Genetic Contributions to Alzheimer's Disease and Frontotemporal Dementia in Admixed Latin American Populations

This study identifies genetic variants associated with Alzheimer's disease and frontotemporal dementia in admixed Latin American populations using whole-genome sequencing and ancestry analysis.

Single Cell Multiomics Across Nine Mammals Reveals Cell Type Specific Regulatory Conservation in the Brain

The paper identifies cell type-specific regulatory elements in nine mammals and shows their conservation and association with neuropsychiatric and neurodegenerative disease risks.

KOLF2.1J iTF-Microglia: A standardized platform to studymicroglial transcriptional regulatory networks in CNS disease

The paper introduces a standardized iPSC-derived microglia model to study transcriptional regulatory networks in CNS diseases and identifies disease-associated genetic variants.

Excitoprotective effects of conditional tau reduction in excitatory neurons and in adulthood

This study generates a conditional tau knockout model and shows that tau reduction in excitatory neurons provides excitoprotective effects, while reduction in inhibitory neurons increases seizure susceptibility, even when induced in adulthood.

Reduced PIN1 gene expression in neocortical and limbic brain regions in female Alzheimer's patients correlates with cognitive and neuropathological phenotypes

The paper finds reduced PIN1 gene expression in female Alzheimer's patients correlates with cognitive decline and neuropathological features, suggesting it as a potential biomarker for AD risk in women.

Domain mapping of disease mutations supports genetic testing of specific SORL1 variants in Alzheimer's Disease

The paper identifies high-priority missense variants in SORL1 associated with increased Alzheimer's Disease risk and earlier onset, suggesting clinical counseling considerations for carriers.

Contributions of rare and common variation to early-onset and atypical dementia risk

The paper analyzes genomic data from early-onset and atypical dementia patients to show that both rare and common genetic variations contribute to dementia risk.

MAPT expression is mediated by long-range interactions with cis-regulatory elements

The paper identifies cis-regulatory elements (cCREs) controlling MAPT expression and links genetic variation in these elements to Alzheimer's disease risk.

Single nucleus multiomics identifies ZEB1 and MAFB as candidate regulators of Alzheimer's disease-specific cis regulatory elements.

Aberrant regulation of a poison exon caused by a non-coding variant in Scn1a-associated epileptic encephalopathy

This study identifies a non-coding variant in SCN1A that causes aberrant inclusion of a poison exon, leading to reduced Nav1.1 expression and Dravet syndrome in a mouse model.

PEA15 loss of function and defective cerebral development in the domestic cat

This study identifies a PEA15 mutation in domestic cats causing lissencephaly and cerebral malformations, revealing a role for PEA15 in gyrencephalic brain development.

Alzheimer's disease risk gene BIN1 induces Tau-dependent network hyperexcitability

This study shows that increased BIN1 expression in neurons leads to hyperexcitability, which is modulated by Tau, suggesting a role for BIN1 in Alzheimer's disease pathogenesis.

Non-Coding and Loss-of-Function Coding Variants in TET2 are Associated with Multiple Neurodegenerative Diseases

The paper identifies rare variants in TET2 associated with early-onset Alzheimer's disease and frontotemporal dementia, highlighting both coding and non-coding variants as risk factors.

Genome sequencing for early-onset dementia: high diagnostic yield and frequent observation of multiple contributory alleles

Genome sequencing for early-onset dementia identified genetic variants in 50% of patients, including pathogenic variants and moderate penetrance alleles, supporting an oligogenic model.

A peptide inhibitor of Tau-SH3 interactions ameliorates amyloid-β toxicity

The paper develops a peptide inhibitor of Tau-SH3 interactions and shows it reduces Aβ oligomer toxicity in neurons.

Genomic diagnosis for children with intellectual disability and/or developmental delay

This study analyzes genomic data from 371 children with intellectual disability or developmental delay to identify pathogenic variants and assess diagnostic utility.