title: Alzheimer culprits: cellular crossroads and interplay.
abstract: Alzheimer's disease (AD) is the primary cause of dementia in the elderly and one of the major health problems worldwide. Since its first description by Alois Alzheimer in 1907, noticeable but insufficient scientific comprehension of this complex pathology has been achieved. All the research that has been pursued takes origin from the identification of the pathological hallmarks in the forms of amyloid-β (Aβ) deposits (plaques), and aggregated hyperphosphorylated tau protein filaments (named neurofibrillary tangles). Since this discovery, many hypotheses have been proposed to explain the origin of the pathology. The "amyloid cascade hypothesis" is the most accredited theory. The mechanism suggested to be one of the initial causes of AD is an imbalance between the production and the clearance of Aβ peptides. Therefore, Amyloid Precursor Protein (APP) synthesis, trafficking and metabolism producing either the toxic Aβ peptide via the amyloidogenic pathway or the sAPPα fragment via the non amyloidogenic pathway have become appealing subjects of study. Being able to reduce the formation of the toxic Aβ peptides is obviously an immediate approach in the trial to prevent AD. The following review summarizes the most relevant discoveries in the field of the last decades.
authors.affiliation: CNRS, UMR-5203, Institut de Génomique Fonctionnelle, F-34000 Montpellier, France. sylvie.claeysen@igf.cnrs.fr
authors.forename: Sylvie
authors.initials: S
authors.lastname: Claeysen
authors.forename: Maud
authors.initials: M
authors.lastname: Cochet
authors.forename: Romain
authors.initials: R
authors.lastname: Donneger
authors.forename: Aline
authors.initials: A
authors.lastname: Dumuis
authors.forename: Joël
authors.initials: J
authors.lastname: Bockaert
authors.forename: Patrizia
authors.initials: P
authors.lastname: Giannoni
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans
chemical_list: D016564:Amyloid beta-Protein Precursor; D053829:Amyloid Precursor Protein Secretases