AD-GPT: large language models in Alzheimer’s disease
Year: 2026
Type: article
Abstract: BACKGROUND: Alzheimer's disease (AD) research produces extensive genomic and clinical data, yet general large language models (LLMs) often generate inaccurate or superficial outputs. We introduce AD-GPT, a domain-specific framework for reliable information retrieval and synthesis of AD-related knowledge. METHODS: We integrated curated genomic resources, including cis-eQTL and sQTL data across 13 brain regions from GTEx, genomic location information from NCBI, and gene function annotations from OMIM, together with approximately 150,000 AD-related publications from NCBI's PubMed. AD-GPT adopts a retrieval-augmented generation (RAG) workflow with task-specific database partitioning, a BERT-based query router, and fine-tuned Llama models, augmented with router and context verifiers to validate task assignment and evidence relevance, supporting three tasks: genetic information retrieval, association study reasoning, and general AD-related knowledge synthesis. RESULTS: AD-GPT consistently outperformed strong baseline LLMs in evidence-grounded evaluation metrics across all tasks, including factual consistency, citation validity, and instruction-level faithfulness. Task-specific retrieval and stacked routing improved evidence grounding and substantially reduced hallucination in complex AD-related queries. CONCLUSION: AD-GPT harmonizes curated genomic databases with biomedical literature, offering a scalable and accurate informatics tool to advance AD research.
Authors: Ziyu Liu, Lintao Tang, Zeliang Sun, Zhengliang Liu, Yanjun Lyu, Wei Ruan, Yangshuang Xu, Liang Shan, Jiyoon Shin, Xiaohe Chen, Dajiang Zhu, Tianming Liu, Rongjie Liu, Chao Huang
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,990
OpenAlex ID: W4415976912