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chanisms of susceptibility and protec- approach, integrated into a long-stan-
tion, as well as their potential role in ding research strategy focused on un-
the spread of the pathology. The first derstanding neurodegeneration, and
objective builds on results from the specifically AD. The project will provide
previous project (SAF2016-78603-R) crucial information on the functional
and also exploits genetic data from the relationship between the development
ongoing GWAS with samples from the of tau pathology, lipid metabolism and
Vallecas project volunteers. membrane dynamics. The described
experimental strategy could eventua-
lly be easily extended to other studies
The first objective will identify new and risk factors/protection from AD
risk factors related to the duration of and other tauopathies. Identifying the
the disease, the rate of progression biological effects of these key factors
and the age of onset. For this purpo- in AD in preclinical studies is essential
se, with the available genetic data, for the development of evidence-ba-
we will perform association analysis sed therapies.
with special emphasis on the poten- • Dementia Genetics Spanish
tial interaction with APOE haplotypes. Consortium (DEGESCO).
We will also validate and functionally
characterize some miRNAs previously Likewise, the CIEN Foundation con-
identified as biomarkers of mild cog- tinues its active participation in the
nitive impairment and AD. The second Dementia Genetics Spanish Consor-
objective focuses on the identification tium (DEGESCO) and in this context,
of the resilience mechanism in cogniti- research activities aimed at defining
vely intact people over 80 years of age. new genetic risk factors and the parti-
For this purpose, we will study genetic cipation of the national consortium in
factors, hallmarks of aging, neurode- international proposals continue to be
generation markers, and structural carried out. Samples from the Vallecas
determinants of resilience in our AD Project and the CAFRS Research Pro-
case-control cohorts. The last objective gram have been used in genome-wide
addresses the role of specific risk/pro- genetic association studies (GWAS).
tection pathways in cell-to-cell spread These association studies, in addition
of tau pathology using cell and animal to serving as a replica in a Spanish po-
models. In addition, we will analyze the pulation of studies carried out in other
expression and localization of proteins populations, will allow us to determine
that modulate tau pathology in brain the most important genetic factors in
tissue. the development of cognitive dysfunc-
tion in our Vallecas Project population,
This project follows a multidisciplinary
