Background: Limited information is yet available on the genetic architecture of Alzheimer's Disease (AD) biomarkers in non-demented subjects. In 2014 we started the EMIF-AD Twin60+ study in which we collected an extensive set of AD amyloid and neuronal injury biomarkers in 98 cognitively healthy elderly monozygotic twin pairs from the Netherlands Twin Register. We aim to assess the predictive value of early AD biomarkers in this healthy group and to determine the resemblance in monozygotic twins, especially by multivariate modeling to get insight into the etiology of comorbidity among markers. Here we present the first results of our study on the monozygotic twin similarity for a range of these biomarkers.
Methods: Twin correlations were calculated for continuous data obtained for amyloid pathology as assessed on [18F] Flutemetamol positron emission tomography (PET) scans and in cerebrospinal fluid (CSF), hippocampal volume and cortical thinning as estimated using Freesurfer, functional connectivity on resting state networks as measured with functional magnetic resonance imaging (fMRI), white matter hyperintensities, structural gray matter connectivity constructed from structural MRI and memory tests.
Results: We found moderate to high correlations in monozygotic twins (58% female, average age 70.2 ± 7.3), with correlations of 0.54 for amyloid pathology measured on PET and in CSF, 0.78 for hippocampal volume, 0.54 for cortical thickness, 0.41 for resting state network connectivity, 0.76 for white matter hyperintensities, 0.67 for structural gray matter connectivity and 0.52 for memory tests.
Conclusions: Even after more than 60 years of life, there are substantial similarities in monozygotic twins for amyloid and neuronal injury markers. This indicates that genetic factors are likely to play an important role in AD pathophysiology. However, resemblance is less than 100% indicating a role for non-genetic factors as well. Next steps include the study of non-genetic risk factors, including epigenetics, lifestyle, vascular comorbidity and inflammation status. These mechanisms may explain the difference in AD markers within monozygotic twin pairs. Unraveling the mechanisms underlying monozygotic twin differences, may eventually lead to the discovery of early treatment targets and preventative strategies for AD.
This work has received support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking EMIF grant agreement n°115372.
Aging , Cognition: Education, Intelligence, Memory, Attention
