title: Neurodegeneration and Alzheimer's disease: the lesson from tauopathies.
abstract: The Amyloid Cascade Hypothesis suggests that the decisive event in Alzheimer's disease (AD) is the deposition of fibrils of beta-amyloid protein (Abeta). The main objection to this hypothesis is the weak correlation between plaque load and severity of dementia. The good correlation between synaptic loss and dementia suggests that AD may be regarded as a synaptic failure. The toxicity of Abeta depends on its state of aggregation. The most important implication derived from the studies of tau gene mutations in a familial form of frontotemporal dementia (FTDP-17) is that the mutation itself is sufficient to cause neuronal loss. Several recent data suggest that apoptotic mechanisms may represent the missing link between Abeta deposition and proteolysis of tau, an early event in the pathogenic sequence of AD. Collectively, these observations suggest a model of AD whereby overproduction or reduced clearance of Abeta initiates a cascade of events that lead to neuronal loss directly or through post-translational modification of tau.
authors.affiliation: University of Naples Parthenope, Via Acton 38, I-80133 Naples, Italy. giuseppe.sorrentino@uniparthenope.it
authors.forename: G
authors.initials: G
authors.lastname: Sorrentino
authors.forename: V
authors.initials: V
authors.lastname: Bonavita
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003704:Dementia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D009154:Mutation / Q000235:genetics; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D024801:Tauopathies / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016875:tau Proteins