CNC.IBILI

Neuro7 | Main Goals

The main goal of this group is the identification of new biomarkers of aging and brain disorders leading to the design of patient-tailored preventive and therapeutic interventions, promoting the translation to the clinic of fundamental research. We will focus on four domains: aging, dementia, neurodegeneration and cognition. In such complex processes a profile of several markers will be necessary to fulfill the criteria of surrogacy. This can only be achieved by the combination of molecular, genetic and biochemical approaches and “-OMICs” research, associated with clinical and neuropsychological evaluation. This group harbors the required know-how, as well as the methodological expertise to achieve this purpose at the human level with access to patients and human biological samples. The opportunity to work in a close collaboration with new groups at CNC.IBILI, and with the imaging unit at ICNAS, will support our goal on the identification of early biomarkers of accelerated aging and rapidly progressive neurodegeneration.Ultimately, we intend to construct patients and biomarkers data basis and propose medical algorithms, integrating new identified biomarkers, in order to help in patient management. Based on previously published work by group members and on results from on-going projects, our specific objectives are:

1 – To identify new risk factors of aging and cognitive decline to the improve quality of life in the elderly
Information on the profile of aging-related risk factors based in cognitive and functional anthropometric characterization will be collected. Biochemical, genetic and epigenetic parameters, associated with oxidative stress, inflammation and metabolic dysfunction, will be evaluated and correlated with age-dependent cognitive decline. We will take advantage of a community-based sample representative of the Portuguese population previously identified by some Group members. The results will contribute to establish innovative approaches and policies to promote a healthy longevity.

2- To identify neurodegenerative diseases biomarkers to improve differential diagnosis accuracy
Biological markers (genetic and biochemical) that specifically reflect the onset of pathology will be assessed in patients with neurodegenerative diseases: Alzheimer’s Disease, Frontotemporal Lobar Degeneration, Parkinson’s Disease, Amyotrophic Lateral Sclerosis and Multiple Sclerosis. Assay platforms will be developed as tools for diagnosis in the prodromal phase of disease, when an early therapeutic intervention will be successful. This will help to elucidate the unsolved clinical, genetic and pathological heterogeneity observed in these disorders that seriously affect the efficacy and outcome of clinical trials.

3– To perform an early diagnosis of dementia towards a successful therapeutic strategy.
Biological samples (CSF, DNA, serum, plasma) of patients/families with various forms of dementia will be studied through a multidisciplinary approach, from genomics to clinics and neuropathology. This will increase the knowledge of the different stages of dementia, including prodromic manifestations, like Delirium and Mild Cognitive Impairment, generating tools for diagnosis, prognosis and progression markers, crucial for planning patient’s assistance and management of economic resources.

4- To identify new diagnosis strategies of accelerated aging, early life cognitive dysfunction and neuropsychiatric disorders.
New biomarkers, starting in the prenatal context, will be identified and validated. By correlating biomarkers with cognitive dysfunction and/or neuropsychiatric phenotypes, namely schizophrenia and bipolar disorder, new diagnosis strategies will be established. We will go from chromosome structure and whole genome studies to biological function using OMICs approaches. Progeria syndromes and Down syndrome will be used as models of aging and cognitive impairment, respectively.