Amino Acids

, Volume 45, Issue 6, pp 1373–1383 | Cite as

Wide distribution of CREM immunoreactivity in adult and fetal human brain, with an increased expression in dentate gyrus neurons of Alzheimer’s as compared to normal aging brains

  • Hans-Gert BernsteinEmail author
  • Elmar Kirches
  • Bernhard Bogerts
  • Uwe Lendeckel
  • Gerburg Keilhoff
  • Marina Zempeltzi
  • Johann Steiner
  • Klaus Tenbrock
  • Henrik Dobrowolny
  • Vasileios C. Kyttaris
  • Christian Mawrin
Original Article


Human cyclic AMP response modulator proteins (CREMs) are encoded by the CREM gene, which generates 30 or more different CREM protein isoforms. They are members of the leucine zipper protein superfamily of nuclear transcription factors. CREM proteins are known to be implicated in a plethora of important cellular processes within the CNS. Amazingly, little is known about their cellular and regional distribution in the brain, however. Therefore, we studied by means of immunohistochemistry and Western blotting the expression patterns of CREM in developing and adult human brain, as well as in brains of Alzheimer’s disease patients. CREM immunoreactivity was found to be widely but unevenly distributed in the adult human brain. Its localization was confined to neurons. In immature human brains, CREM multiple neuroblasts and radial glia cells expressed CREM. In Alzheimer’s brain, we found an increased cellular expression of CREM in dentate gyrus neurons as compared to controls. We discuss our results with regard to the putative roles of CREM in brain development and in cognition.


CREM Adult human brain Developing human brain Alzheimer’s disease Immunohistochemistry Western blot 


Beta amyloid


Alzheimer’s disease


Also known as


Amyloid precursor protein


CREM/activating transcription factor


Brodmann area


Cyclic adenosine monophosphate


Central nervous system


cAMP response element


cAMP response element-binding protein


cAMP response element modulator




Dentate gyrus


Ethylene diamine tetraacetic acid


Ethylene glycol tetraacetic acid


Inducible cAMP early repressor


Immunoglobulin G


Leucine-charged residue-rich domains


Sodium dodecyl sulfate


Leucine zipper (protein superfamily)



The skillful technical work of Leona Bück, Ines Schellhase, Sandra Hartmann, Bianca Jerzykiewicz and Nadine Klappoth is highly appreciated.

Conflict of interest

The authors declare no conflict of interest.


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Copyright information

© Springer-Verlag Wien 2013

Authors and Affiliations

  • Hans-Gert Bernstein
    • 1
    Email author
  • Elmar Kirches
    • 2
  • Bernhard Bogerts
    • 1
  • Uwe Lendeckel
    • 3
  • Gerburg Keilhoff
    • 4
  • Marina Zempeltzi
    • 1
  • Johann Steiner
    • 1
  • Klaus Tenbrock
    • 5
  • Henrik Dobrowolny
    • 1
  • Vasileios C. Kyttaris
    • 6
  • Christian Mawrin
    • 2
  1. 1.Department of PsychiatryOtto-von-Guericke-UniversityMagdeburgGermany
  2. 2.Departments of NeuropathologyOtto-von-Guericke-UniversityMagdeburgGermany
  3. 3.Department of Biochemistry and Molecular BiologyUniversity of GreifswaldGreifswaldGermany
  4. 4.Institute of Biochemistry and Cell BiologyOtto-von-Guericke-UniversityMagdeburgGermany
  5. 5.Department of PediatricsRWTH AachenAachenGermany
  6. 6.Division of Rheumatology, Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonUSA

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