Senescence is the markup of events related to the exit of the cell cycle by some cells due to various factors, and accumulation of such senescent cells leads to the onset of aging, but when it occurs at early stages, it becomes the cause of many age-related pathologies. Many factors can be responsible for such events, such as oxidative stress, DNA damage, telomere shortening, and overexpression of lysosomal β-gal, forming it into senescence-associated β-gal (SA-β-gal). These cells activate the apoptotic pathway involving apoptotic factors like p53-p21-16 and begin to secrete pro-inflammatory factors like chemokines and cytokines, making other adjacent cells tumorigenic, thus leading to senescence-associated secretory phenotype (SASP). In another turn of events, due to some reasons, the folding process of proteins by cytosolic chaperones or in ER gets interrupted, causing the hydrophobic amino acids to come to the surface, but such misfolded proteins further undergo ubiquitinylation and proteasomal degradation. In case misfolded proteins do not get degraded, they then aggregate and form amyloid fibrils, especially in neurons, leading to various neurodegenerative diseases such as α-synuclein in the case of Alzheimer’s and Parkinson’s. The current chapter deals with cellular senescence and various neurodegenerative disorders other than Alzheimer’s and Parkinson’s and the mechanism and techniques of their diagnosis.