Learning From Cognitively Healthy Centenarians to Escape Alzheimer's Disease

We aim to explore the characteristics and mechanisms of resistance and resilience that lead to the escape of dementia until extreme ages using blood-based biomarkers. Aim 1: In-depth assessment of the correlation between the load of post-mortem AD-associated neuropathology in the brain and concentrations of AD-associated biomarkers in blood. Aim 2: Evaluation of the blood-biomarker loads in blood samples from centenarians who are resistant or resilient against AD and centenarians who are cognitively declined. Aim 3: Identifying the AD-genetic variants associated with blood-biomarker profiles for resistance or resilience against AD-pathology.

Aim 1: In-depth assessment of the correlation between the load of post-mortem AD-associated neuropathology in the brain and concentrations of AD-associated biomarkers in blood. Aim 2: Evaluation of the blood-biomarker loads in blood samples from centenarians who are resistant or resilient against AD and centenarians who are cognitively declined. Aim 3: Identifying the AD-genetic variants associated with blood-biomarker profiles for resistance or resilience against AD-pathology.

We have collected myriad biomaterials, including blood and brain samples and longitudinal cognitive testing data, from a unique cohort of >400 cognitively healthy centenarians who have successfully escaped or delayed the onset of AD until extreme ages. Assessing the blood samples from this group, using state-of-the-art blood based biomarkers will provide us with completely unique new insights about resilience or resistance against AD-associated risk factors.

With the outcome of the comparisons between matched blood and brain measurements, we will publish regression models that translate between blood biomarker values and brain pathology stages.

We will generate blood-biomarker profiles of resistance and resilient centenarians and associate these with survival, cognitive performance and lifestyle factors.

We will associate genetic variants with the blood-biomarker profiles of resistance or resilience to further investigate underlying pathways and mechanisms.