Amyloid (Aβ) pathology precedes clinical dementia by decades. So far it remains unclear to what extent genetic and environmental influences play a role in Aβ deposition. Studies in monozygotic twins are useful to estimate the upper-limit of genetic contribution to a disease. Earlier studies in twins have focused on concordance of clinical Alzheimer’s Disease (AD)-type dementia, but no twin studies have not been performed on the presence of Aβ pathology. The aim of this study is to estimate the concordance of regional Aβ load between cognitively healthy elderly monozygotic twin pairs.


      We selected the first 46 monozygotic twin pairs from the NTR-EMIF-AD PreclinAD study, which aims to enroll 100 twin pairs. Inclusion criteria were age ≥60 years and delayed recall score above -1.5 SD of normative data. Dynamic [18F]flutemetamol (FMM) scans were performed with combined data from two scans (30 minutes starting directly after FMM injection and 90-110 minutes post injection). With cerebellar grey matter as reference region non-displaceable binding potential (BPND) in the anterior and posterior cingulate cortex (ACC and PCC) was calculated using the basis function implementation of the simplified reference tissue model (RPM1). Amyloid load was compared using correlation matrices with Pearson’s correlation.


      Subjects were on average 65.1 (IQR 62-73) years old and (67%) were female. They had 15 (SD 4.3) years of education and a MMSE score of 29 (IQR 29-30). Median FMM binding in ACC was 0.24 (IQR 0.19-0.33) BPND and in the PCC 0.25 (IQR 0.20-0.33) BPND. For the BPND in the ACC we found a correlation of 0.5 and for the PCC 0.6, see figure 1, both p <0.01. After correction for age and gender the correlation was 0.44 for ACC and 0.51 for PCC (both p < 0.01).


      We found a significant correlation between monozygotic twins for regional Aβ BPND with an upper limit for genetic influences on total variance of 50-60%, which is larger than in reports on clinical AD-type dementia (20-59%) in twins. Our data suggests a strong genetic background for Aβ pathology in cognitively healthy elderly although non-genetic factors also influence Aβ aggregation. Supported by EU/EFPIA IMI EMIF n°115372.
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      Figure 1Correlation between Flutemetamol BPND in Posterior Cingulate Cortex in Twin 1 (x-axis) and Twin 2 (y-axis)