Reelin-immunoreactive Cajal-Retzius cells: the entorhinal cortex in normal aging and Alzheimer's disease.
Alzheimer's disease (AD) is a disorder of brain self organization associated with morphodysregulation at the synaptic level. Disturbances follow a hierarchical spatio-temporal pattern throughout the cortex and involve the re-activation of developmental molecular programs. The large glycoprotein reelin, synthesized by Cajal-Retzius (CR) cells, is an important component of a signaling pathway involved in embryonic development and modulation of synaptic circuitry, but is also implicated in the pathogenetic cascade in AD. Although the majority of CR cells sequentially disappears from the postnatal cortical layer I, a few of them persist in the normal adult brain. They continue to produce reelin, express a variety of other proteins, and are characterized by a typical morphology. Recently, CR cells have been reported to be altered in number and morphology in a variety of neurological and psychiatric diseases linked to maldevelopment. In the present study we show that reelin-positive CR cells persist in the layer I of the entorhinal cortex in normal senescent brains and are also preserved in AD. The majority of CR cells in AD is morphologically and cytochemically-as revealed by double labeling with calcium-binding proteins-indistinguishable from normal cases, suggesting that they are not dramatically altered in the entorhinal cortex of AD patients. Nevertheless, CR cells seem to be partially affected by the formation of paired helical filaments, indicating subtle changes that are suggested to be a result rather than a cause of the pathogenetic cascade of AD.
Riedel
Anett
A
Department of Neuroanatomy, Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, 04109 Leipzig, Germany. rieda@medizin.uni-leipzig.de
Miettinen
Riitta
R
Stieler
Jens
J
Mikkonen
Mia
M
Alafuzoff
Irina
I
Soininen
Hilkka
H
Arendt
Thomas
T
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002452:Cell Count; D002552:Cerebral Ventricles / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D018728:Entorhinal Cortex / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D000091042:Reelin Protein; D012697:Serine Endopeptidases
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; C085349:PHF-1 monoclonal antibody; D000091042:Reelin Protein; C043697:calcium-binding protein (brain); C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases