CDKN1A and Alzheimer disease: In mouse models, critically short telomeres, which directly trigger telomeric DDR (tDDR) activation, have been shown to worsen AD pathology (Suelves et al, 2023), and loss of p21, a CDK inhibitor induced by DNA damage, can rescue cognitive deficits and neuronal dysfunction in mice with shortened telomeres (Jurk et al, 2012).