0-TESTO COMPLETO.pdf - Fondazione Santa Lucia

Sezione III: Attività per progetti
specificity and reproducibility for the determination of Ab40, Ab42, total tau
and phospho-tau concentrations in CSF. These results will be transferred to
the Alzheimer Centers of the Italian NHS and disseminated to the scientific
community.
WP2. The objective is to validate recently identified peripheral biochemical
(CSF and plasma) markers for AD diagnosis in order to generate a multivariate
molecular protocol that have higher sensitivity/specificity compared to
the basic protocol analyzed in WP1. A particular effort will be made trying to
find whether these parameters can help in distinguishing the MCI patients
who will develop AD from those who will not convert to dementia.
The following markers will be investigated:
1) Ab oligomers;
2) Ab truncated fragments;
3) cystatin C (whole molecule and truncated forms);
4) NGF and pro/NGF;
5) a battery of chemokynes and other pro- or anti-inflammatory mediators.
WP3. The objective is to validate genetic markers that have recently identified
and that may act as risk factors for developing AD, as well as for the
conversion of MCI to AD.
The following markers will be investigated:
1) allelic variants of gene involved in Ab processing as sortilin-related
receptor 1 (SORL1), kinesin, insulin degrading enzyme (IDE), neprylysin and
in cholesterol metabolism as cholesterol 24S-hydroxylase (CYP46) and APOE;
2) haplotype B of cystatin C gene;
3) haplotype H1c of MAPT gene;
4) allelic variants of gene involved in inflammatory response (progranulin
– PGRN, and chemokine-cluster in proximity to PGRN in chromosome 17).
WP4. The objective is to establish a network of banks that ensure storage
of high quality samples of biological material (DNA, serum and cell lines)
from patients with cognitive deterioration at different stages and nondemented
control collected under standard conditions. The network will
develop a common database containing key informations on clinical, neurophysiological
and imaging data.
This will supply a valuable source of well-characterized specimens for the
present project and for future studies
GENERAL TRANSFERIBILITY AND POTENTIAL IMPACT OF RESULTS
This project will establish a multivariate molecular protocol having high
sensitivity, specificity and reproducibility for the early diagnosis of Alzheimer
disease at a pre-dementia stage.
In particular the study is designed to:
a) define standard operating procedures for CSF analysis of already
known biomarkers (i.e., Ab, total tau and phospho-tau),
702 2009