O3-02-03: association between apoe isoform and 18-month tau accumulation

The ε4 isoform of the apolipoprotein gene (APOE) has been established as a risk-factor for development of both early and late-onset Alzheimer's Dementia (AD). Substantial evidence suggests ε4 carriers accumulate amyloid and demonstrate cognitive deficits at an earlier age than non-carriers. ε4 carriers also have higher tau neurofibrillary tangle stage at autopsy and increased in vivo CSF tau-measures compared to non-carriers. Herein we examine 18-month change in tau signal using flortaucipir PET between ε4 carriers and non-carriers. Data on 185 subjects (147 AD, 37 Mild Cognitive Impairment, 1 Cognitively Normal) was pooled from phase II-III studies of flortaucipir and from the Expedition 3 trial of solanezumab, where no solanezumab-treatment interaction on flortaucipir was observed. SUVr was assessed in temporal lobe composite (entorhinal cortex, fusiform, parahippocampal, and inferior temporal gyri) and weighted-cortical (MUBADA) VOIs relative to a parametrically-derived white matter reference region (PERSI). Included subjects were both amyloid positive (visually positive florbetapir PET scan) and tau positive (temporal lobe SUVr > 2.5 SDs above the mean of n=16 young controls). Subject demographics are in Tables 1 (with) and 2 (without) solanezumab-treated subjects. Tau SUVr was assessed at baseline and 18 months. ε4 carriers were younger than non-carriers in a gene-dose dependent order (p=0.00002) while amyloid SUVr (p=0.07) and MMSE (p=0.16) were similar between groups. Baseline tau SUVr was highest for ε4 homozygotes (p=0.02). Trends remained similar when removing solanezumab treated subjects from all groups. When controlling for baseline SUVr and age, there was a significant effect of APOE (p=0.0286) as well as a baseline SUVr by APOE interaction (0.0039) on 18-month tau change (Table 3). Post hoc analysis indicated that 18-month change in tau signal followed a gene-dose dependent order (p=0.0003).