In the supplement we propose to partner with the ENIGMA APOE2 working group, led by Paul Thompson, to uncover the structural and functional network changes associated with the protective factor of apolipoprotein variant ?2, which occurs in approximately 8% of the population. We will also evaluate the relationship of brain measure to apathy and anhedonia within each APOE variant (which has also shown to be protective against mood disorders) and identify common and unique aspects in our mental illness cohorts. To do this we will develop a decentralized statistical testing framework for decentralized multivariate analysis with group independent component analysis (ICA) and also an enhanced data fusion approach. This will enable us to evaluate, in thousands of individuals, the unique structural and functional signatures of individuals with the protective APOE variant and the profiles of negative symptoms and their relationship to profiles of these symptoms in mental illness assessed within the parent R01.
In this supplement we propose to partner with the ENIGMA APOE2 working group to implement decentralized analysis of resting fMRI and structural MRI data, separately and jointly, in a large data set. APOE2 has been shown to be protective of Alzheimer?s, but the neurobiology of individuals with this variant has not been well characterized. We will study the distribution of these brain imaging measures within APOE subgroups and to negative symptoms measures which we believe will provide an important window into Alzheimer?s disease and Alzheimer?s related disorders.
