β-Amyloid precursor protein and tau protein levels are differently regulated in human cerebellum compared to brain regions vulnerable to Alzheimer's type neurodegeneration.

It is well established that the human brain exhibits regional variability in its vulnerability to Alzheimer's disease (AD) pathology. We set out to determine if this regional vulnerability is reflected in the expression pattern, or processing, of two key proteins involved in AD pathology, the β-amyloid precursor protein (APP) and tau, by immunoblotting. Our data demonstrate that APP processing and APP protein levels are not different between AD patients and healthy, age-matched subjects, but that levels of mature APP are greatly reduced in cerebellum compared to regions of the brain most vulnerable to AD, entorhinal cortex and hippocampus. In addition, protein levels of tau are significantly reduced in cerebellum compared to all other human brain regions examined. Unexpectedly, protein levels of glycogen synthase kinase 3 (GSK3), a major tau kinase, are at their lowest in hippocampus. The observations demonstrate that both mature APP as well as total APP and tau protein levels are greatly reduced in human cerebellum, a region of the human brain most resistant to AD pathology.