Alzheimer's amyloid-β and tau protein accumulation is associated with decreased expression of the LDL receptor-associated protein in human brain tissue

Introduction: One of the major neuropathological features of Alzheimer's disease (AD) is the accumulation of amyloid-β (Aβ) protein in the brain. Evidence suggests that the low-density lipoprotein receptor-associated protein (RAP) binds strongly to Aβ and enhances its cellular uptake and that decreased RAP expression correlates with increased Aβ production in animal models of AD. Methods: The current study examined whether RAP levels change in AD human brain tissue and whether they are related to the amount of AD pathology. RAP and NeuN levels were determined by Western blot, while low-density lipoprotein receptor-related protein 1 (LRP1), tau and Aβ levels were determined by ELISA in the temporal cortex of 17 AD and 16 control cases. Results: An increase in total Aβ and insoluble and soluble tau protein was observed in AD brain tissue. In contrast, RAP levels were significantly decreased in AD brain tissue compared to controls. Correlation analysis revealed that levels of RAP correlated with both total Aβ and soluble and insoluble tau levels. Neither LRP1 nor NeuN levels were significantly altered in AD brain tissue homogenates and did not correlate with Aβ or tau protein levels. Conclusion: Reduction in RAP may contribute to the accumulation and aggregation of Aβ in the AD brain