In this study, using a comprehensive 'cocktail antibody' approach 51, we discovered that CCH predominantly affects NDUFS8-marked mitochondrial complex I, leading to mitochondrial damage in the basal forebrain without abnormal of mitochondrial complex II - V. Crucially, we found deregulating NDUFS8 elicited impaired spatial memory of normal rats, while upregulating NDUFS8 prevented CCH-induced cognitive decline of 2VO rats. Here, NDUFS8 is linked to columnar cell hyperplasia of the breast.