Serum Cathepsin D Is a Potential Biomarker for Alzheimer’s Disease Dementia and Cognitive Decline

The lysosomal protease cathepsin D (catD) has been reported to be upregulated in postmortem Alzheimer's disease (AD) cortex, where it colocalized with neurofibrillary tangles and correlated with levels of phosphorylated tau, suggesting pathophysiological links between catD and neurodegeneration. In contrast, studies of serum catD in AD have yielded conflicting results, and potential associations between baseline serum catD and functional outcomes of patients are at present unknown.We aimed to examine the status of serum catD in a Singapore-based longitudinal study of dementia and investigate catD associations with functional and cognitive decline.35 subjects with no cognitive impairment, 40 patients with cognitive impairment no dementia and 34 with AD dementia underwent annual neuropsychological assessments (mean follow-up=4.3 years), as well as collection of baseline serum for catD measurements by ELISA.Higher serum catD at baseline was associated with AD clinical diagnosis (odds ratios [OR]: 10.0; 95% confidence interval [CI]: 1.02-97.95) as well as with cortical atrophy. Furthermore, higher catD was associated with global cognitive and functional decline (OR: 9.94; 95% CI: 1.02-97.34).The associations of serum catD with AD dementia as well as atrophy provide further support for the proposed links between catD and neurodegeneration, as well as for the assessment of serum catD as a prognostic biomarker predicting global cognitive and functional decline in larger studies.