Page 58 - Annual Report 2018

3.2.5. Department of Molecular Genetics mentia phase. This evolution is largely determined by
genetic risk variants and is associated with bioche-
The aging of the population and the growing epi- mical changes that can ideally serve as early mar-
demic of Alzheimer's disease (AD) highlight the im- kers of the disease.
portance of research in the molecular mechanisms
of pathology, as well as in the development of me- Department activities
thods for the early detection of the disease to carry
out an adequate evaluation of risk and to be able to The activity of the Molecular Genetics Department
implement early and effective therapies. Currently, it focuses mainly on the search for biomarkers of early
is widely accepted that changes at the cellular level diagnosis of Alzheimer's disease and the study of ge-
associated with AD, including the formation of neu- netic susceptibility factors of AD and other neuro-
rofibrillary plaques and tangles, begin many years degenerative disorders. This activity has the following
before clinical symptoms are evident or the exis- objectives: to deepen the molecular basis of the di-
tence significant cell death in the brain. Therefore, sease and develop predictive algorithms that com-
the development of biomarkers that allow the iden- bine information on genetic and biochemical
tification of patients with incipient AD or asympto- markers with diagnostic, prognostic or response
matic people at risk is of great importance, so that value to modifying therapies.
treatments aimed at stopping neurodegeneration
can be initiated before it becomes irreversible. For this purpose, multidisciplinary research with the
rest of the CIEN Foundation departments, together
The most extensively studied biochemical markers with the CIEN Tissue Bank (BT-CIEN), are decisive for
are the tau protein (total levels and different phos- working on the two main projects of the CIEN Foun-
phorylated isoforms) and the amyloid β peptide in dation-Queen Sofia Foundation: the Vallecas Pro-
cerebrospinal fluid (CSF), that are both directly rela- ject for the early detection of Alzheimer's disease
ted to neurofibrillary and amyloid pathology, res- and the Alzheimer's Center of the Queen Sofia Foun-
pectively. However, the drawbacks derived from dation Research Program.
obtaining CSF, together with a limited precision of
these assays in early phases, highlight the need to The Vallecas Project
identify new markers, in particular in more accessi-
ble biological fluids such as blood. Currently, many It is currently known that the pathological processes
researchers believe that both the development of that determine Alzheimer begin many years before
neurofibrillary and amyloid pathologies in AD repre- the disease leads to the first noticeable symptoms in
sent relatively late events in the evolution of the di- patients. Years before that future drug treatments
sease, which may or may not reflect the preventing or slowing down disease progression
fundamental biochemical-molecular dysfunctions could be applied to the "population at risk" who has
that give rise to the disease. The clinical manifesta- developed these subclinical lesions, or has a higher
tions of AD are preceded by an asymptomatic pre- risk of developing it than the rest of the population.
clinical phase, after which the first symptoms appear In this context it is framed the Vallecas Project, which
in the prodromal phase of the disease characterized is constituted as a 5-year longitudinal study specifi-
by mild cognitive impairment (MCI). In this sense, AD cally aimed at discovering the factors that would
can be understood as a continuous process that allow us to detect this "population at risk" in a phase
evolves from the asymptomatic phases to the de- of potentially treatable pathology.

CIEN Foundation Annual Report 2018 / 58