PGP and Alzheimer disease: Interestingly, double-knockout P-gp null mice (mdr1 a/b−−) have increased A-beta amyloid accumulation in the brain, possibly linking reduced P-gp function to AD pathology.4, 43 Similar results have been seen using a P-gp blocker to abolish P-gp function in the BBB on APPswe mice, a type of mice that overexpress human amyloid precursor protein, with a mutation that causes an autosomal dominant form of early-onset familial AD.4, 43