However, direct evidence supporting a role for p16Ink4a in brain physiology is still deficient and is mostly supported by circumstantial evidence, including the involvement of p53 and Rb moieties in response to brain trauma, aetiology of neurodegenerative diseases or cancer [43,44,45,46,47,48,49,50]. This evidence concerns the gene CDKN2A and neurodegenerative disease.