Accurate diagnosis of Alzheimer's disease (AD) in Memory Clinics remains challenging due to the limited specificity of conventional clinical assessment and structural imaging. The recent commentary by Vyhnalek and colleagues advocates for the incorporation of molecular biomarkers for AD diagnosis in clinical practice. However, this approach only partially captures the complexity of disease expression due to co-pathologies such as limbic-predominant age-related TDP-43 encephalopathy, a mimic of AD. At the era of immunotherapy for AD, clinical expertise remains essential to identify AD from its mimics, especially when both entities co-exist, and may rely on advanced neuroimaging techniques such as brain connectivity.