A study of 31 patients with primary progressive aphasia (PPA) identified three distinct clinical variants: nonfluent progressive aphasia (NFPA), semantic dementia (SD), and logopenic progressive aphasia (LPA). Each variant was associated with specific patterns of brain atrophy. NFPA, characterized by speech difficulties and syntactic processing issues, showed atrophy in the left inferior frontal and insular regions. SD, marked by fluent speech and semantic memory deficits, had anterior temporal lobe atrophy. LPA, with slow speech and syntactic comprehension issues, showed atrophy in the left posterior temporal cortex and inferior parietal lobule. Genetic analysis revealed higher APOE ε4 haplotype frequency in LPA (67%) compared to NFPA (20%) and SD (0%). These findings suggest different underlying pathological processes for each variant. PPA is often the first symptom of neurodegenerative diseases like frontotemporal lobar degeneration (FTLD) and corticobasal degeneration (CBD). The study highlights the importance of comprehensive cognitive, neuroimaging, and genetic assessments to differentiate PPA variants and understand their distinct pathologies. The results emphasize the heterogeneity of PPA and the need for further research to confirm these findings.A study of 31 patients with primary progressive aphasia (PPA) identified three distinct clinical variants: nonfluent progressive aphasia (NFPA), semantic dementia (SD), and logopenic progressive aphasia (LPA). Each variant was associated with specific patterns of brain atrophy. NFPA, characterized by speech difficulties and syntactic processing issues, showed atrophy in the left inferior frontal and insular regions. SD, marked by fluent speech and semantic memory deficits, had anterior temporal lobe atrophy. LPA, with slow speech and syntactic comprehension issues, showed atrophy in the left posterior temporal cortex and inferior parietal lobule. Genetic analysis revealed higher APOE ε4 haplotype frequency in LPA (67%) compared to NFPA (20%) and SD (0%). These findings suggest different underlying pathological processes for each variant. PPA is often the first symptom of neurodegenerative diseases like frontotemporal lobar degeneration (FTLD) and corticobasal degeneration (CBD). The study highlights the importance of comprehensive cognitive, neuroimaging, and genetic assessments to differentiate PPA variants and understand their distinct pathologies. The results emphasize the heterogeneity of PPA and the need for further research to confirm these findings.