Chronic Neurodegenerative Disorders (CNDs) represent a progressive and irreversible group of neurological conditions characterized by sustained neuronal injury, synaptic dysfunction, and gradual structural degeneration of the central and peripheral nervous systems, ultimately leading to cognitive, motor, sensory, and autonomic impairment. The nervous system’s unique microanatomy-comprising neurons, glial cells, synapses, myelinated and unmyelinated fibers, and specialized neurovascular units-undergoes sequential structural remodeling during the course of chronic neurodegeneration. Early alterations predominantly involve functional and ultrastructural changes at the neuronal and synaptic level, including mitochondrial dysfunction, oxidative stress, impaired axonal transport, and synaptic loss, while advanced stages are marked by neuronal death, gliosis, demyelination, and gross anatomical atrophy of specific brain and spinal cord regions. Understanding the applied anatomy of neurons and their relationships with astrocytes, oligodendrocytes, microglia, and cerebral vasculature is essential for correlating structural damage with clinical manifestations, biochemical abnormalities, and neuroimaging findings in chronic neurodegenerative disorders. This review analyzes the applied neuroanatomy with emphasis on neuron-centered structural changes observed in chronic neurodegeneration, integrating evidence from neuropathology, imaging studies, and contemporary neurological literature. Structural alterations at the cellular, tract, and regional levels are correlated with functional consequences such as cognitive decline, movement disorders, sensory deficits, autonomic dysfunction, and behavioral changes. Radiological features including cortical and subcortical atrophy, ventricular enlargement, white matter changes, and regional signal alterations reflect underlying neuronal loss and progressive architectural disintegration. An integrated understanding of neuroanatomy, histology, and imaging provides a comprehensive framework for early diagnosis, disease classification, prognostication, and effective management of Chronic Neurodegenerative Disorders.