A prominent feature in many neurodegenerative diseases involves the spread of the pathology from the initial site of damage to anatomically and functionally connected regions of the central nervous system (CNS), referred to as transsynaptic degeneration (TSD). This review covers the possible mechanisms of both retrograde and anterograde TSD in various age-related neurodegenerative diseases, including synaptically and glial mediated changes contributing to TDS and their potential as therapeutic targets. This phenomenon is well documented in clinical and experimental studies spanning various neurodegenerative diseases and their respective models, with a significant emphasis on the visual pathway, to be explored herein. With the increase in the aging population and subsequent rise in age-related neurodegenerative diseases, it is crucial to understand the underlying mechanisms of.