PROJECT SUMMARY Primary Progressive Aphasia (PPA) is a clinical syndrome characterized by isolated progressive loss speech and language functions due to selective degeneration of language networks. Nearly all past PPA research has focused on English language speakers, even though there are an estimated 1.2 billion native Chinese speakers worldwide and 3.5 million Chinese speakers in the United States. Considering the comparable prevalence of PPA in the Caucasians and Chinese-American population, there might be more than a million Chinese PPA individuals worldwide. The majority of them remain unidentified or misdiagnosed, largely due to the lack of appropriate assessment tools and lack of awareness. Chinese-speaking PPA individuals are mainly assessed by speech and language tools translated verbatim from the English language. This is inadequate as it does not account for the profound linguistics differences between English and Chinese language. Through the joint effort of researchers, clinicians, and speech-language pathologists from the US, Taiwan, and Hong Kong, we developed a neuroanatomically-based and linguistically-adapted Chinese language assessment battery for PPA (CLAP). The CLAP battery's feasibility has been demonstrated through a pilot project funded by U.S. Alzheimer's Association and Global Brain Health Institute. The overarching goal of this project is to improve the clinical diagnosis and classification of Chinese-speaking PPA patients. This project consists of two specific aims. The first aim focuses on validating the neuroanatomical specificity of the individual tests in the CLAP battery. Through this effort, we will acquire in-depth anatomical knowledge of various neurolinguistics components in the Chinese speaking population. The second aim is designed to investigate the clinical and linguistics features of imaging-based phenotypes in our Chinese PPA cohort. Enrolled Chinese-speaking PPA individuals will be clustered into different imaging-based phenotypes based on their predominant atrophy areas. The MRI volumetric phenotypes will be compared between the Chinese-speaking and English-speaking cohorts to validate the PPA neuroimaging signatures. The clinical and linguistics features of each imaging based phenotype will be studied to identify significant key features that facilitate the diagnosis and classification of the Chinese-speaking PPA population. This project will provide novel mechanistic insights to the neural basis of language in Chinese speakers and establish specific speech and language assessment tools for the Chinese-speaking PPA population with the long-term goal of improving diagnosis and care for this underserved population. It also promotes linguistics diversity in the field of neurodegenerative disease research.