title: Decisive role of Reelin signaling during early stages of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is one of the largest unmet medical concerns of our society. Around 25 million patients worldwide together with their families are still waiting for an effective treatment. We have recently initiated a re-evaluation of our knowledge of the molecular and cellular mechanisms underlying sporadic AD. Based on the existing literature, we have proposed a mechanistic explanation of how the late-onset form of the disease may evolve on the cellular level. Here, we expand this hypothesis by addressing the pathophysiological changes underlying the early and almost invariant appearance of the neurofibrillary tangles, the only reliable correlate of the cognitive status, in distinct brain areas and their consistent "spread" along interconnected neurons as the disease advances. In this review we present and discuss novel evidence that the extracellular signaling protein Reelin, expressed along the olfactory and limbic pathways in the adult brain, might hold a key to understand the earliest steps of the disease, highlighting the olfactory pathway as the brain's Achilles heel involved in the initiation of the pathophysiological characteristic of late-onset AD.
authors: Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, Switzerland.
authors: D
authors: D
authors: Krstic
authors: S
authors: S
authors: Pfister
authors: T
authors: T
authors: Notter
authors: I
authors: I
authors: Knuesel
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D015816:Cell Adhesion Molecules, Neuronal / Q000502:physiology*; D042241:Early Diagnosis; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D006801:Humans; D008032:Limbic System / Q000378:metabolism / Q000473:pathology; D009415:Nerve Net / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009833:Olfactory Pathways / Q000378:metabolism / Q000473:pathology; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717127:RELN protein, human; D012697:Serine Endopeptidases