Alzheimer disease (AD) is characterized by the abnormal deposition of amyloid-beta (Aβ) plaques and tau tangles in neurons and glia. Although Aβ correlates well with disease, abnormal, tau accumulation is thought to be a major factor contributing to neurodegeneration in AD. Increasing data indicate that that specific Rab proteins malfunction in affected brain regions in AD. Nearly 70 Rab GTPase proteins have been identified in humans. Rab proteins play an important role in intracellular trafficking, endocytosis, and exocytosis/secretion; and may contribute to clearance of abnormally aggregated proteins including tau. Altered Rab function may be a precursor to tau protein accumulation, aggregation, and associated AD and AD-related pathology. Among several Rab proteins, both Rab8a and Rab35 have emerging roles in Parkinson disease (PD) and AD pathophysiology. In PD Rab35 levels are high in serum and in brain regions affected by disease, implying a role in disease pathology.

These data provide the first evidence that Rab8a and Rab35 may regulate tau levels and associated pathology.