Decreased levels of ARPP-19 and PKA in brains of Down syndrome and Alzheimer's disease

ARPP-19 (cAMP-regulated phosphoprotein of Mr = 19,000) is a substrate for c AMP-dependent protein kinase (PKA). ARPP-19 is found in all brain regions b ut the function of ARPP-19 is not fully elucidated yet. We detected a downr egulated sequence with 100% homology with ARPP-19 in temporal cortex of pat ients with Down syndrome (DS) as compared to controls, but not in Alzheimer 's disease (AD) using differential displaypolymerase chain reaction (DD-PCR ). We subsequently determined protein levels of ARPP-19 in temporal cortex and cerebellum by immunoblotting and observed significant reduction of ARPP -19 in DS (temporal cortex) and AD (cerebellum). We also observed decreased activities of PKA in DS (temporal cortex and cerebellum) and AD (temporal cortex). These findings suggest that decreased ARPP-19 along with decreased activities of PKA is involved in pathomechanisms of both neurodegenerative disorders. Furthermore, these findings provide first evidence for an impai red mechanism of cAMP-related signal transduction and phosphorylation in bo th dementing disorders.