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Neuronal death and processing of Tau protein in Alzheimer's disease

In a research report recently published in the Journal of Alzheimer's Disease (http://www.j-alz.com), published by IOS Press, a research group from the International School for Advanced Studies (ISASSISSA) in Trieste (Luisa Fasulo, Gabriele Ugolini e Antonino Cattaneo) showed that a processed form of tau protein induces neuronal death by apoptosis (programmed cell death) when expressed in cultured rat hippocampal neurons. Pathological changes in the microtubule associated protein tau are a major hallmark of the human dementias collectively defined as tauopathies, including Alzheimer's disease (AD). In Fronto-Temporal Dementia with Parkinsonism linked to Chromosome 17 (FTDP-17), several mutations in the tau gene were identified showing that primary malfunction of tau can lead to neurodegeneration. Such findings shed new light on the role of post-translational modifications of tau protein occurring in other tauopathies (such as AD), including aberrant proteolysis. In AD, tau protein aggregates in intraneuronal deposits known as "neurofibrillary tangles" (NFT), one of the two hallmarks of the disease. Tau molecules normally associate to microtubules (major cytoskeletal structures); in AD, tau proteins dissociate from microtubules and aggregate into NFTs.

Inappropriate neuronal apoptosis (or neuronal cell death) is present in AD, as well as in other neurodegenerative diseases. In a previous study, the authors showed that tau is a substrate for the apoptotic protease caspase-3 (an enzyme involved in cell death processes) and an effector of apoptosis itself, in established cell lines. Moreover, the cleavage of tau by caspase-3 has been recently confirmed to occur "in vivo" in AD brain as an early event. The study shows the apoptotic properties of tau fragments in cultured hippocampal neurons, a neuronal subpopulation precociously affected by AD pathology.

According to the authors, neurodegeneration would be perpetuated b
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Contact: Mauro Scanu
scanu@sissa.it
39-040-378-7557
Case Western Reserve University
15-Mar-2005


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