Cathepsin D

Cathepsin D (CTSD) is an acid protease localized to intracellular compartments that mediates protein breakdown, including APP processing following ADAM30-mediated cleavage, which directs APP toward degradation (UniProt: P07339). The enzyme is involved in lysosomal catabolism and has been implicated in the pathogenesis of neurodegenerative storage diseases, notably ceroid lipofuscinosis neuronal type 10 (CLN10, MIM 610127), characterized by progressive neurodegeneration and lysosomal accumulation of autofluorescent material.

In Alzheimer's Disease, Cathepsin D is upregulated in post-mortem human AD brain tissue compared to age-matched controls, as measured by TMT-labeled quantitative proteomics across subcellular fractions (Chaparral AD proteomics; mean log2FC: +0.61). This elevation is consistent with the protein's known involvement in amyloid-β precursor protein (APP) metabolism, supporting a disease-relevant role in AD pathogenesis, although the functional consequence of increased protease activity in the AD brain remains to be fully characterized.