Immunohistochemical analyses have further revealed intensified CTSS distribution in Aβ-positive plaques and τ-positive tangle-bearing neurons in Alzheimer's disease brain sections [17], indicating that elevated CTSS levels might disrupt physiological homeostasis in the microenvironment and contribute to pathological changes as well as cognitive impairment in the CNS. Here, CTSS is linked to early-onset autosomal dominant Alzheimer disease.