Abstract: Alzheimer’s disease (AD) is the most common cause of dementia, characterized by progressive cognitive decline, and affects over 55 million people worldwide. AD is pathological featured by the aberrant accumulation of amyloid-β plaques, neurofibrillary tangles formed by hyperphosphorylated tau, synaptic loss, and dysfunction of neurotransmitter systems. Evidence from in vivo and autopsy studies has consistently shown that synaptic dysfunction and loss are strongly correlated with cognitive decline in AD, particularly in brain regions such as the hippocampus and cortex, which are critical for memory formation and processing. This perspective highlights recent histopathological findings related to synaptic dysfunction in AD, advancements in the development of imaging and fluid-based biomarkers for synaptic loss, and future studies.