Normal Brain Ageing, Alzheimer's Disease and the Role of Apolipoproteins

Description

Blood is not only a repository for a variety of disease biomarkers, but its constituents can also reflect the status of the body as it ages, responds to lifestyle and environmental impacts such as nutrition, exercise and education, and reflects changes within the body such as response to disease. While current blood-based assays of specific markers such as Aβ peptides have been disappointing, there is a wealth of as yet untapped information in blood which holds promise to:

Distinguish profiles of normal ageing from disease trajectories,
Identify biochemical targets for lifestyle intervention, and
Identify potential causative and/ or protective factors for disease onset.

To date, we have used cutting edge proteomics technology to identify dysregulation of several plasma protein family groups in mild cognitive impairment (MCI) and Alzheimer’s Disease (AD). We have found that levels of apolipoprotein family members are correlated with cognition scores, brain volume measures and blood lipids.

Aims

We focus on six apolipoproteins (representative of each of the apolipoprotein storage/carrier compartments) to assess their post-translation modifications (PTMs) (phosphorylation, oxidation and glycation).

We hypothesise that:

Specific structural changes to the apolipoprotein family members will distinguish individuals who age normally from those with Alzheimer’s Disease (AD) or Mild Cognitive Impairment (MCI). In particular, increased oxidative modification of plasma apolipoproteins will be apparent in AD and MCI.
Apolipoproteins have specific modifications which regulate their function, in particular phosphorylation. The pattern of apolipoprotein phosphorylation will vary between normal ageing and individuals with AD and MCI.