APP-695 transcript prevalence is selectively reduced during Alzheimer's disease in cortex and hippocampus but not in cerebellum.

We previously found a selective loss of the brain specific APP-695 transcript in Alzheimer's disease (AD) cortex, which results in a 2.5-fold increase in the APP-751/APP-695 transcript ratio in AD (9). Here we report a similar increase in APP-751/APP-695 mRNA ratio in AD hippocampus. However, the cerebellum had a 6-fold lower ratio, which does not change in AD. The APP-695 mRNA species is greatly decreased (3-4-fold) in mRNA from AD cortex and hippocampus, whereas the APP-751 mRNA species is essentially unchanged. Considering hippocampal neuron loss and cortical neuron loss and atrophy, the data presented may be compatible with increased APP-751 mRNA and decreased APP-695 mRNA prevalence in remaining neurons in AD. A possible relationship between a high APP-751/APP-695 ratio and amyloid pathology is discussed.