Identification of age-related Human Blood factors as a therapeutic target for Alzheimer's disease

One of the most exciting findings in neuroscience has been the discovery of peripheral blood factors with rejuvenating or ageing effects on the mouse brain.

These factors were discovered by parabiosis experiments in which the blood circulation of young and old animals is fused. The findings imply that the properties of young blood can rejuvenate the older brain.

Ageing is the most important risk factor for Alzheimer’s Disease (AD), but there have been only limited attempts to develop therapies targeting the ageing process.

Also, it is not known whether humans have similar blood factors that could be therapeutic targets in AD.The overall aim of the HeBe project is to discover blood factors with a rejuvenating or ageing effect on the human brain that can thus become therapeutic targets for AD and other age-related brain diseases.

For ethical reasons, parabiosis experiments are not possible in humans.

HeBe will circumvent this problem using a highly original approach in which I will define extreme biological age phenotypes in women and men based on the difference between biological and chronological age.

I will use advanced proteomics and metabolomics to identify blood factors that differ between these extreme phenotypes, and then develop a targeted assay toolkit to measure these factors in large longitudinal cohorts of cognitively unimpaired and preclinical AD individuals.The main hypothesis of HeBe is that higher levels of rejuvenating blood factors decrease the rate of neurodegeneration, while higher levels of ageing blood factors increase the rate of neurodegeneration.

If this hypothesis is confirmed, I will provide a new therapeutic target for AD.

By the end of HeBe, I will also design a proof-of-concept clinical trial to assess whether life-style or pharmacological interventions modify blood levels of rejuvenating or ageing factors.

Thus, the HeBe project is the first and a key step in the translational continuum towards interventions in clinical practice.