title: Reelin depletion is an early phenomenon of Alzheimer's pathology.
abstract: Alterations in the expression of Reelin (RELN) have been implicated in the pathology of Alzheimer's disease (AD). However, whether these changes are cause or consequence of AD remains to be resolved. To better understand the role of RELN pathway in the development of AD, we examined the expression profile of RELN and its downstream signaling members APOER2, VLDLR, and DAB1 in AD-vulnerable regions of transgenic and wildtype mice as well as in AD patients and controls across disease stages and/or aging. We show that both AD pathology and aging are associated with perturbation of the RELN pathway in a species-, region-, and molecule-specific manner. Further, we show that depletion of RELN, but not its downstream signaling molecules, is detectable long before the onset of amyloid-β pathology in the murine hippocampus and in a pre-clinical AD stage in the human frontal cortex. This early event hints at a possible causative role of RELN decline in the precipitation of AD pathology and supports RELN's potential as a pre-clinical marker for AD.
authors.affiliation: Institute of Pathology and Neuropathology, University Hospital Essen, Essen, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Herring
authors.forename: Anja
authors.initials: A
authors.lastname: Donath
authors.forename: Katharina M
authors.initials: KM
authors.lastname: Steiner
authors.forename: Manuel P
authors.initials: MP
authors.lastname: Widera
authors.forename: Samira
authors.initials: S
authors.lastname: Hamzehian
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Kanakis
authors.forename: Konrad
authors.initials: K
authors.lastname: Kölble
authors.forename: Ayman
authors.initials: A
authors.lastname: ElAli
authors.forename: Dirk M
authors.initials: DM
authors.lastname: Hermann
authors.forename: Werner
authors.initials: W
authors.lastname: Paulus
authors.forename: Kathy
authors.initials: K
authors.lastname: Keyvani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D042241:Early Diagnosis; D016326:Extracellular Matrix Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
chemical_list: D015415:Biomarkers; 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