title: Reelin immunoreactivity in neuritic varicosities in the human hippocampal formation of non-demented subjects and Alzheimer's disease patients.
abstract: BACKGROUND
  Reelin and its downstream signaling members are important modulators of actin and microtubule cytoskeleton dynamics, a fundamental prerequisite for proper neurodevelopment and adult neuronal functions. Reductions in Reelin levels have been suggested to contribute to Alzheimer's disease (AD) pathophysiology. We have previously reported an age-related reduction in Reelin levels and its accumulation in neuritic varicosities along the olfactory-limbic tracts, which correlated with cognitive impairments in aged mice. Here, we aimed to investigate whether a similar Reelin-associated neuropathology is observed in the aged human hippocampus and whether it correlated with dementia status.
  
  
  RESULTS
  Our immunohistochemical stainings revealed the presence of N- and C-terminus-containing Reelin fragments in corpora amylacea (CAm), aging-associated spherical deposits. The density of these deposits was increased in the molecular layer of the subiculum of AD compared to non-demented individuals. Despite the limitation of a small sample size, our evaluation of several neuronal and glial markers indicates that the presence of Reelin in CAm might be related to aging-associated impairments in neuronal transport leading to accumulation of organelles and protein metabolites in neuritic varicosities, as previously suggested by the findings and discussions in rodents and primates.
  
  
  CONCLUSIONS
  Our results indicate that aging- and disease-associated changes in Reelin levels and proteolytic processing might play a role in the formation of CAm by altering cytoskeletal dynamics. However, its presence may also be an indicator of a degenerative state of neuritic compartments.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, Zurich, CH-8057, Switzerland. knuesel@pharma.uzh.ch.
authors.forename: Tina
authors.initials: T
authors.lastname: Notter
authors.forename: Irene
authors.initials: I
authors.lastname: Knuesel
mesh_terms: D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism; D015153:Blotting, Western; D015816:Cell Adhesion Molecules, Neuronal / Q000134:cerebrospinal fluid / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000134:cerebrospinal fluid / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D017628:Microglia / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000134:cerebrospinal fluid / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000134:cerebrospinal fluid / Q000378:metabolism*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases