Abstract:Large language models (LLMs) have emerged as powerful tools for medical information retrieval, yet their accuracy and depth remain limited in specialized domains such as Alzheimer's disease (AD), a growing global health challenge. To address this gap, we introduce AD-GPT, a domain-specific generative pre-trained transformer designed to enhance the retrieval and analysis of AD-related genetic and neurobiological information. AD-GPT integrates diverse biomedical data sources, including potential AD-associated genes, molecular genetic information, and key gene variants linked to brain regions. We develop a stacked LLM architecture combining Llama3 and BERT, optimized for four critical tasks in AD research: (1) genetic information retrieval, (2) gene-brain region relationship assessment, (3) gene-AD relationship analysis, and (4) brain region-AD relationship mapping. Comparative evaluations against state-of-the-art LLMs demonstrate AD-GPT's superior precision and reliability across these tasks, underscoring its potential as a robust and specialized AI tool for advancing AD research and biomarker discovery.