TWIN CORRELATIONS FOR AMYLOID PATHOLOGY MEASURED WITH POSITRON EMISSION TOMOGRAPHY AND IN CEREBROSPINAL FLUID IN COGNITIVELY HEALTHY ELDERLY MONOZYGOTIC TWIN PAIRS

Abstract

Amyloid (Aß) pathology precedes Alzheimer's Disease dementia (AD) by decades. It is unclear to what extent genetic and environmental influences play a role in Aß pathology. Twin studies showed monozygotic (MZ) twin concordance for AD-dementia of around 0.8 but estimates for Aß pathology are lacking. Aß can be measured on positron emission tomography (PET) scans and in cerebrospinal fluid (CSF). This study aims to compare the genetic contribution to Aβ on PET and in CSF and to test the association between these modalities in cognitively healthy elderly MZ twins. MZ twins were selected from the EMIF-AD PreclinAD study. Inclusion criteria were age ≥60 years and delayed recall score above -1.5 SD of normative data. Dynamic [18F]flutemetamol (FMM) scans were performed on a Philips PETMRI system with specific binding (BPND) as outcome. In CSF we measured Aβ1–42, which decreases in AD as result of Aβ aggregation, and Aβ1–40, which only slightly changes in AD, using ADx Neurosciences/Euroimmun. Within twin pair correlations of Aβ pathology were calculated using Pearson's correlation, the association between Aβ on PET and in CSF was calculated using generalized estimating equations. We included 94 twin pairs and 5 individual twins (total 193 subjects), with a mean age of 70.4±7.5 years, of which 116 had CSF available (mean global PET Aβ=0.16±0.13, CSF Aβ1–42=868±298 and Aβ1–40=9476±2853 pg/mL). Twin correlations were 0.47 for global PET Aβ and 0.60 for CSF Aβ1–42, 0.82 for Aβ1–40, and 0.68 for ratio Aβ1–42/Aβ1–40, figure 1–2. We found a negative association between global Aβ on PET and Aβ1–42 in CSF (r=-0.373; p<0.001, figure 3).