Expression of ataxin-2 in brains from normal individuals and patients with Alzheimer's disease and spinocerebellar ataxia 2

Spinocerebellar ataxia type 2 (SCA2) is caused by expansion of a CAG trinucleotide repeat located in the coding region of the human SCA2 gene. The SCA2 gene product, ataxin‐2, is a basic protein with two domains (Sm1 and Sm2) implicated in RNA splicing and protein interaction. However, the wild‐type function of ataxin‐2 is yet to be determined. To help clarify the function of ataxin‐2, we produced antibodies to three antigenic peptides of ataxin‐2 and analyzed the expression pattern of ataxin‐2 in normal and SCA2 adult brains and cerebellum at different developmental stages. These studies revealed that (1) both wild‐type and mutant forms of ataxin‐2 were synthesized; (2) the wild‐type ataxin‐2 was localized in the cytoplasm in specific neuronal groups with strong labeling of Purkinje cells; (3) the level of ataxin‐2 increased with age in Purkinje cells of normal individuals; and (4) ataxin‐2‐like immunoreactivity in SCA2 brain tissues was more intense than in normal brain tissues, and intranuclear ubiquitinated inclusions were not seen in SCA2 brain tissues. Ann Neurol 1999;45:232–241