Single-nucleus multi-omics identifies shared and distinct pathways in Pick’s and Alzheimer’s disease

The study of neurodegenerative diseases, particularly tauopathies like Pick’s disease (PiD) and Alzheimer’s disease (AD), offers insights into the underlying regulatory mechanisms. By investigating transcriptomic and epigenomic variations in these conditions, we identified critical regulatory changes driving disease progression, revealing potential therapeutic targets. Our comparative analyses uncovered disease-enriched non-coding regions and genome-wide transcription factor (TF) binding differences, linking them to target genes. Notably, we identified a distal human-gained enhancer (HGE) associated with E3 ubiquitin ligase (UBE3A), highlighting disease-specific regulatory alterations. Additionally, fine-mapping of AD risk genes uncovered loci enriched in microglial enhancers and accessible in other cell types. Shared and distinct TF binding patterns were observed in neurons and glial cells across PiD and AD. We validated our findings using CRISPR to excise a predicted enhancer region i..., , , # Single-nucleus multi-omics identifies shared and distinct pathways in Pick’s and Alzheimer’s disease

[https://doi.org/10.5061/dryad.h9w0vt4t9](https://doi.org/10.5061/dryad.h9w0vt4t9)

## Description of the data and file structure

| Tab | Information |
| :------- | :------------------------------------------------------------------------------------------------------ |
| tableS1A | metadata for PiD and AD  |
| tableS1B | snATAC-seq FindAllMarkers on Gene Activity  |
| tableS1C | cell counts for each celltype in snATAC-seq and snRNA-seq |
| tableS1D | snRNA-seq FindAllMarkers on Gene Expression  |
| tableS2A | a complete peakset of snATAC-seq for bo..., All human tissue samples used in this study were obtained from brain banks with appropriate institutional ethical approval and informed consent from donors or their legal representatives. Consent included permission for de-identified data to be shared publicly.

To ensure compliance with data protection policies, all personally identifiable information (PII) has been removed. Metadata fields that could potentially be used to identify individuals—such as Brainbank name, exact Age, Sample ID, and Postmortem Interval (PMI)—have been masked or anonymized in the accompanying metadata and README file.

This dataset contains only de-identified data and is shared in accordance with the ethical standards of the contributing institutions and the data sharing policy of DataDryad.org.