We report the first autopsy case of genetically confirmed, autosomal-dominant chorea-acanthocytosis (AD-ChAc), showing a heterozygous mutation (G-A) at nucleotide position 8,295 in exon 57 of VPS13A. The patient was a 36-year-old Japanese man and the duration of his illness was 11 years. Neuropathologically, the patient showed marked atrophy and neuronal loss, particularly small and medium-sized neurons, with astrocytic gliosis in the caudate nucleus, putamen and globus pallidus. These findings were similar to previous autopsy reports of autosomal-recessive ChAc (AR-ChAc) with mutations of VPS13A. The broad distribution of atrophic neurons and astrocytosis throughout the whole brain was unique in our AD-ChAc patient and has not been described in AR-ChAc. The neuronal density of the dorsal caudate nucleus was lower than that of the ventral side in this patient as well as in three Huntington's disease (HD) patients. The neuronal densities in both the rostral and caudal sides were lower than that in the middle region at the anterior commissure level, while in the three HD patients, the neuronal densities of the caudate nucleus were more decreased in the caudal side. This ChAc patient showed faint immunoreactivity in the caudate nucleus and globus pallidus with antibodies against the striatal neurotransmitters, methionine-enkephalin, leucine-enkephalin and substance P. The difference in patterns of neuronal vulnerability could reflect those in the mechanisms of neurodegeneration between ChAc and HD.