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.

神经退行性疾病的研究，尤其是Pick病（PiD）与阿尔茨海默病（AD）这类tau蛋白病（tauopathies），可为其潜在调控机制提供重要见解。通过分析此类疾病的转录组（transcriptomic）与表观基因组（epigenomic）变异，我们鉴定出驱动疾病进展的关键调控变化，进而揭示潜在治疗靶点。本研究的比较分析揭示了疾病富集的非编码区域及全基因组范围内的转录因子（TF）结合差异，并将其与靶基因建立关联。值得注意的是，我们鉴定出一个与E3泛素连接酶（UBE3A）相关的人类特异性远端增强子（HGE），凸显了疾病特异性的调控改变。此外，对AD风险基因的精细定位发现，其位点富集于小胶质细胞增强子区域，并在其他细胞类型中具有染色质可及性。在PiD与AD的神经元与神经胶质细胞中，观察到了共享与独特的转录因子结合模式。我们利用成簇规律间隔短回文重复序列（CRISPR）技术切除预测的增强子区域以验证研究发现……

# 单细胞核多组学揭示Pick病与阿尔茨海默病中共存与独特的通路

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

## 数据与文件结构说明

| 表格编号 | 信息内容 |
| :------- | :----------------------------------------------------------------------- |
| tableS1A | Pick病与阿尔茨海默病的元数据 |
| tableS1B | 基于基因活性的单细胞核转座酶可及性测序（snATAC-seq）FindAllMarkers分析结果 |
| tableS1C | 单细胞核转座酶可及性测序（snATAC-seq）与单细胞核RNA测序（snRNA-seq）各细胞类型的细胞计数 |
| tableS1D | 基于基因表达的单细胞核RNA测序（snRNA-seq）FindAllMarkers分析结果 |
| tableS2A | 单细胞核转座酶可及性测序（snATAC-seq）的完整峰集（peakset）……

本研究所有人体组织样本均来自脑库，且已获得机构伦理审查委员会批准以及供体或其法定代理人的知情同意。同意书中包含允许将去标识化数据公开共享的条款。为遵守数据保护政策，所有个人可识别信息（PII）均已完成移除。在附带的元数据与README文件中，所有可能用于识别个体的元数据字段——如脑库名称、具体年龄、样本ID、死后间隔时间（PMI）——均已进行掩码或匿名化处理。本数据集仅包含去标识化数据，其共享遵循贡献机构的伦理标准及DataDryad.org的数据共享政策。