title: The Amyloid Cascade Hypothesis in Alzheimer's Disease: It's Time to Change Our Mind.
abstract: Since its discovery in 1984, the beta amyloid peptide has treaded the boards of neurosciences as the star molecule in Alzheimer's disease pathogenesis. In the last decade, however, this vision has been challenged by evidence-based medicine showing the almost complete failure of clinical trials that experimented anti-amyloid therapies with great hopes. Moreover, data have accumulated which clearly indicate that this small peptide plays a key role in the physiological processes of memory formation. In the present review, we will discuss the different aspects of the amyloid cascade hypothesis, highlighting its pros and cons, and we will analyse the results of the therapeutic approaches attempted to date that should change the direction of Alzheimer's disease research in the future.
authors.affiliation: Department of Experimental Medicine, Section of General Pathology, University of Genova, Genova, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Ricciarelli
authors.affiliation: Department of Pharmacy, Section of Pharmacology and Toxicology, University of Genova, Genova, Italy.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Fedele
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D006801:Humans
chemical_list: D016229:Amyloid beta-Peptides
keywords: Alzheimer's disease; LTP; anti-amyloid therapy; beta amyloid; clinical trials; memory