HAGH and Alzheimer disease: In the AD group, downregulated genes in Exc in level 1 spots were associated with responses to mitochondrial dysfunction (e.g., UQCRQ, ATP6V1G2, POLR2F), oxidative stress (e.g., PTGES3, MT3, HAGH), and protein clearance (e.g., PSMD8, CHMP4B, VPS4A), suggesting greater functional impairment in Exc near large vessels in AD (Fig. 5C).