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Genetic and environmental contributions to amyloid burden in older Australians: a PiB-PET imaging study of twins

Dr Melissa Slavin, Prof Christopher Rowe, Professor Julian Trollor, Prof Perminder Sachdev, Prof Henry Brodaty
Research Centre DCRC Assessment and Better Care
Partner Institution
Project Description

Beta-amyloid (AB) plaques are one of the hallmark neuropathologies of Alzheimer's disease (AD), yet their aetiology is not understood. Converging evidence from autosomal dominant mutations, study of Down's syndrome patients, family studies and the known risk of the APOE E4 allele suggests that genetic factors are important. However environmental factors appear to also make an important contribution. Amyloid burden can now be assessed in vivo using positron emission tomography with the Pittsburgh compound B ([11C]PiB-PET), making it possible to examine the relationship between AB burden and cognitive deficits in temporal proximity. Potential moderating factors such as genetics or environment need to be considered however. 

Twins offer a powerful strategy to differentiate the relative contributions of genetic and environmental factors, as monozygotic (MZ) twins share 100% of their genes while dizygotic (DZ) twins share only 50%. Our group has unique access to a cohort of elderly MZ and DZ twins who are participating in the longitudinal Older Australian Twins Study (OATS). This cohort has already had extensive medical, neuropsychiatric, and structural brain imaging assessments. 

We will invite a subset of this cohort to participate in a separate PiB-PET imaging study to determine their amyloid burden, and calculate the heritability of amyloid plaques. We will also calculate genetic and environmental factors that may be contributing to the relationship between amyloid burden and cognition. The current project will be a 10 twin-pair pilot study for this larger study, which is outlined in the Research Plan. 

There are two major aims of this project: 

  1. To determine the relative contribution of genetic and environmental factors to AB deposition in the brains of older Australians; and 
  2. To determine whether discordant cognitive functioning in MZ twins can be explained on the basis of differential AB deposition in the brain, and determine the environmental factors that explain these differences.
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