0-TESTO COMPLETO.pdf - Fondazione Santa Lucia

Sezione III: Attività per progetti
LIST OF PARTICIPATING UNITS
U.O.1 – U.O. di Neuropatologia, Fondazione IRCCS Istituto Neurologico
Carlo Besta, Milano – Fabrizio Tagliavini
U.O.2 – Laboratorio di Neurogenetica, IRCCS S. Giovanni di Dio –
Fatebenefratelli, Brescia – Giuliano Binetti
U.O.3 – Laboratorio di Neuropsicobiologia, IRCCS Fondazione Santa Lucia,
Roma – Paola Bossù
U.O.4 – Direzione Scientifica, European Brain Research Institute, Roma –
Antonino Cattaneo
U.O.5 – Dipartimento di Biologia Cellulare e Neuroscienze,
Istituto Superiore di Sanità, Roma – Annamaria Confaloni
U.O.6 – Laboratorio di Biochimica delle Proteine, Istituto Mario Negri,
Milano – Mario Salmona
U.O.7 – U.O. Malattie Neurodegenerative, IRCCS Fondazione Ospedale
Maggiore Policlinico, Milano – Daniela Galimberti
U.O.8 – Dipartimento di Neuroscienze, Università di Genova –
Massimo Tabaton
DESCRIPTION OF THE PROJECT
What is already known on the subject
The research on biochemical markers of Alzheimer’s disease (AD) has
been focused primarily on the molecules that play a central role in the
pathogenesis, i.e. the amyloid-beta protein (Ab), particularly the Ab42 isoform,
and the tau protein. These studies demonstrated that the cerebrospinal
fluid (CSF) concentrations of Ab42 are reduced while total tau and
phospho-tau concentrations are increased in AD patients in comparison to
non-demented controls. However, similar changes are present in neurological
disorders other than AD such as frontotemporal, Lewy body and vascular
dementia, and the sensitivity and specificity of these parameters, even in
combination, is less then 90%, with marked variability among different
studies [Hansonn et al. (2006) Lancet Neurol 5:228-234]. The specificity is
even less significant when Ab42 and tau levels are used to predict the conversion
of MCI to AD.
Since at least three classes of disease-modifying therapies (including antiamyloid,
neuroprotective and restorative approaches) are anticipated for AD,
it is imperative to find additional markers that, in combination with those
currently used, allow to increase the diagnostic specificity and sensitivity of
incipient or prodromal AD. On this ground, several proteomic studies have
been performed on biological fluids, yielding to the identification of some
CSF (Simonsen et al. (2007) Neurobiol Aging online] and plasmatic markers
[Ray et al. (2007) Nat Med 13:1359-1362] that are differentially expressed in
AD and MCI in comparison to controls. Among these markers, Cystatin C
700 2009