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RF07.39.1 – Genetic risk factors and peripheral biological markers of conversion from Mild…
U.O. 3 – Laboratorio di Neuropsicobiologia
Paola Bossù
Specific contribution of the Unit to the project
This U.O. will contribute to WP2 and WP4.
WP2. New peripheral biochemical markers of AD and/or predictors of MCI to AD
conversion – Specific aim: to investigate the chemokines and other pro- or
anti-inflammatory mediators dosage in serum and in peripheral blood monocytic
cells as biomarkers for MCI and AD.
Several studies have demonstrated that inflammation plays an important
role in mediating glial alterations and neurodegeneration that occur in AD
patients. This phenomenon includes the accumulation of reactive microglia
and astrocytes in damaged regions of AD brain and increased pro-inflammatory
cytokine expression that may further contribute to the development and
progression of pathological state.
Accordingly, in several studies pro-inflammatory cytokines such as Interleukin
(IL)-1, IL-6, Tumor Necrosis Factor (TNF)-a and IL-18 have been found
to be peripherally increased in AD patients and substantially impaired in the
late stage of the disease. However, the temporal definition of their implication
in respect to disease progression, as well the extent to which inflammatory
factors participate to the neuronal damage are issues of fundamental importance,
which are to date still unclear.
Recent studies performed by this participant unit have identified a possible
role for the pro-inflammatory cytokine IL-18 in AD, by means of genetic
data suggesting that IL-18 gene promoter polymorphisms can predict risk and
outcome of AD, and by demonstrating that IL-18 is overexpressed by blood
cells of AD patients and correlates with their cognitive decline.
In the present study, by using a longitudinal clinical approach, the previous
results regarding IL-18 will be expanded also to other inflammatory mediators
with potential role in the disease progression and pathogenesis. In fact,
this project is aimed to investigate the impact of pro-inflammatory and antiinflammatory
parameters during disease progression in patients at the higher
risk of developing AD, i.e. MCI patients.
These objectives are relevant for the identification of new diagnostic markers
of the AD preclinical form and for the comprehension of inflammatory
mechanisms, likely participating in the earliest pathogenic processes of AD.
WP4. Establishment of a network of banks of biological materials: see U.O.1 for
details.
Methods
Subjects
Fifty people with a diagnosis of MCI, and thirty healthy control subjects,
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