Differential involvement of small G proteins in Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disease characterized by th e progressive deterioration of cognitive function and memory in association with the widespread presence of senile plaques, neurofibrillary tangles an d neuronal cell death. However, its pathophysiology remains unknown. GTP-bi nding proteins with;molecular weights of approximately 20,000 are designate d small G proteins. In the present study we quantitatively analyzed the sma ll G proteins, Ras, Rap, Ral and Rab in brains removed at autopsy from cont rols and AD patients to examine whether small G proteins are equally or dif ferentially affected in AD. Western blot analysis indicated that the protei n level of Ras and RalB in both the cytosolic and membranous fractions and that of Rap2 in the cytosolic fraction was significantly decreased, while t hat of Rab8 in the membranous fraction was significantly increased in AD br ains compared with controls. The protein level of other small G proteins wa s not different between control and AD brains. These results suggest a diff erential involvement of small G proteins in AD.