Proteomics in Mild Cognitive Impairment

Project Outlines and Aims

Using plasma for diagnostic purposes is a popular and low risk approach to evaluating disease markers. One powerful new approach for exploring a broad range of changes to plasma proteins is proteomics. This method utilizes mass spectrometry and protein databases generated from human genome sequencing to identify proteins which are altered in disease. It is a highly versatile technique, which can be used either qualitatively or quantitatively and can help identify structural changes to proteins which result from disease processes. Some biochemical pathways and processes which may be affected/altered in MCI include; inflammation, free radical activity and oxidative stress, abnormal cleavage of peptides and abnormal proteolytic enzyme activity. The main goal of this project is to determine whether disease-related changes can be observed in MCI plasma and whether these could be of diagnostic value or provide insight into disease etiology.

Some of our specific aims include;

1. Discover potential markers for Alzheimer’s disease (AD) diagnosis, particularly in prodromal stages such as mild cognitive impairment (MCI), using proteomics approaches.
2. Discover patterns of protein change MCI plasma which could be of diagnostic value, and also aid in the understanding of disease aetiology.
3. Examine the role of alterations to specific pathways in AD, and find points of commonality between AD and MCI, which may help identify individuals who eventually convert from MCI to AD. Pathways include: (a) inflammation, (b) oxidative stress markers, (c) small molecular weight metabolites/nutrients which may impact on cellular longevity (including nicotinamide, resveratrol, NAD, antioxidants such as flavenoids, vitamins)

Potential Participants

Plasma samples are being obtained from 2 large epidemiological studies as well as a Memory Disorders Clinic:

1. The first study is the Memory and Ageing Study (MAS) which is a study of 70-90 year old individuals in the Randwick area who have been sampled through the electoral roll. These individuals receive a comprehensive neuropsychiatric and medical assessment and are categorized into MCI or normal controls (NC). Dementia is exclusionary for this study. The total sample will be 1200 by Aug 2007, all of whom will donate a blood sample (about 600 subjects have been recruited). This cohort will be followed up 2 years later with repeat assessments, and diagnostic determination.
2. The second study is the PATH Through Life Study which has 3 cohorts (20-24, 40-44 and 60-64). The cohort of interest is the 60+ cohort. While the total sample comprises about 2500, about 450 individuals were randomly chosen for blood samples and MRI scans. They were also assessed from a neuropsychiatric viewpoint. This sample has had 2 assessments, 4 years apart, and has donated 2 blood samples. Diagnoses of MCI and NC have been made.

Staff

Prof Perminder Sachdev
A/Prof George Smythe
Ms Anne Poljak
Ms Tharusha Jayasena
Dr Julian Trollor
Prof Henry Brodaty


Back Row (L to R): Lora Ng, George Smythe, DonQing Liu, Perminder Sachdev, Wei Wen.
Front Row (L to R): Xiaohua Chen, Ora Lux, Angie Russell, Anne Poljak