Investigating blood and cerebrospinal fluid biomarkers in autosomal dominant Alzheimer's disease

Pratishtha Chatterjee

    Research output: ThesisDoctoral Thesis

    406 Downloads (Pure)

    Abstract

    [Truncated] Alzheimer's disease (AD) is the most common form of dementia affecting the lives of countless families across the globe. Currently, an AD diagnosis is confirmed by post-mortem autopsy, while pre-mortem biomarkers measured in the cerebrospinal fluid (CSF) or by neuroimaging involve invasive and highly sophisticated techniques which are too expensive for population based screening.

    This study investigated blood constituents in the international Dominantly Inherited Alzheimer Network (DIAN) cohort, with the aim of identifying potential AD biomarkers. Samples were accessed from two of the 12 Centres, one based at the McCusker Alzheimer's Research Foundation (MARF) in Perth and the other at the Mental Health Research Institute(MHRI) in Melbourne. Individuals in this cohort have a biological parent who carries a mutation responsible for autosomal dominant AD (ADAD), thus have a 50% chance of inheriting the mutation.

    Proteomic and lipidomic studies were carried out on samples from ADAD mutation carriers predestined to develop the disease (MC) as well as non-carriers (NC). The study had access to plasma from 44 participants, CSF from 36 participants and platelet samples from 27 participants. Using isobaric tag for relative and absolute quantitation (iTRAQ), relative plasma concentrations of proteins in MC and NC were compared and found to be altered. Additionally, differences in plasma and CSF phospholipid profiles were identified on comparing MC and NC using mass spectrometry, thus establishing altered phospholipid metabolism occurs in ADAD.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Publication statusUnpublished - 2014

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