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Project Topic
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Age represents by far the largest risk factor for dementia, including Alzheimer’s disease (AD) dementia. However, not every person will develop dementia during aging, indicating that age-related processes may not inescapably lead to dementia. The elucidation of the fundamental processes occurring in aging will likely offer new options to prevent or postpone the development of dementia. One such key mechanism is cellular senescence, which causes chronic inflammation through the release of a senescence-associated secretory phenotype (SASP) profile of mediators. PREADAPT will build on the hypothesis that chronic systemic inflammation and neuroinflammation, quantified through a set of SASP mediators, affects the basal trajectory of the senescence occurring in the aging brain, thus allowing to predict future cognitive decline and dementia. The levels and changes of SASP mediators during aging are modulated by different genetic and environmental factors defining thereby a personalized risk for progressing to dementia. Importantly, research has identified that SASP mediators are also altered in cerebrospinal fluid of AD patients. By leveraging the individual variability of large existing aged samples, we aim to integrate SASP, genetics, known AD biomarkers, and comorbidities to generate combined Risk profiles which will provide personalized information on the risk of progression to dementia. To achieve these goals, PREADAPT has gathered a team of leading experts in the field of neuroinflammation, epidemiology, genetics, epigenetics, neuropsychology, and clinical research. PREADAPT has access to state-of-the-art methodology and knowhow on inflammatory markers to define a set of SASP mediators which derived from preliminary research done by PREADAPT members. PREADAPT has also access to large epidemiological and clinical follow-up studies that are characterized in-depth using neuroimaging, genomics, and proteomics. This unique configuration will enable PREADAPT to identify, already at pre-dementia stages, age-related profiles informing on the personalized future risk to decline cognitively and to progress to dementia. From a translational perspective, PREADAPT will also provide first evidence showing that a SASP personalized risk profile responds to a specific intervention.
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