Abstract The silencing of actin capping protein ß2, Capzb2, by RNAi in developing cultured neurons results in short, dystrophic neurites reminiscent of cytoskeletal changes seen in diverse neurodegenerative diseases, including Alzheimer’s disease (AD) and Huntington’s disease (HD). Actin and tubulin are two major cytoskeletal proteins indispensable for normal neurite development and regenerative responses to injury and neurodegenerative stimuli. We have previously shown that Capzb2 binds tubulin and, in the presence of microtubule-associated protein tau, affects microtubule polymerization necessary for neurite outgrowth and normal growth cone morphology. Accordingly, Capzb2 silencing in hippocampal neurons results in short neurites with abnormal growth cones. Decreased neurite length is found in both AD and HD. In the first step towards uncovering the possible role of Capzb2 in these diseases, we studied Capzb2 protein expression in the postmortem brains of AD and HD patients. To determine whether disease-specific changes in Capzb2 protein accompany the progression of neurodegeneration, we performed Western Blot analysis of prefrontal cortices (PFC) and hippocampi (HPC) in AD patients and of PFC and heads of caudate nuclei (HCN) in HD patients. Our results show disease- and areaspecific dynamics in the levels of Capzb2 protein expression in the progressive stages of AD and HD.