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

  • S. H. Kim
  • A. C. Nairn
  • N. Cairns
  • G. Lubec


ARPP-19 (cAMP-regulated phosphoprotein of Mr = 19,000) is a substrate for cAMP-dependent protein kinase (PKA). ARPP-19 is found in all brain regions but the function of ARPP-19 is not fully elucidated yet. We detected a downregulated sequence with 100% homology with ARPP-19 in temporal cortex of patients with Down syndrome (DS) as compared to controls, but not in Alzheimer’s disease (AD) using differential display-polymerase 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 impaired mechanism of cAMP-related signal transduction and phosphorylation in both dementing disorders.


Down Syndrome Adenylyl Cyclase Vasoactive Intestinal Peptide Temporal Cortex cAMP Response Element Bind 
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© Springer-Verlag/Wien 2001

Authors and Affiliations

  • S. H. Kim
    • 1
  • A. C. Nairn
    • 2
  • N. Cairns
    • 3
  • G. Lubec
    • 1
  1. 1.Department of PediatricsUniversity of ViennaAustria
  2. 2.Laboratory of Molecular and Cellular NeuroscienceRockefeller UniversityNew YorkUSA
  3. 3.Institute of Psychiatry, Brain BankKing’s CollegeUK

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