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ApoE4 associated with higher tau accumulation independent of amyloid burden
Author(s) -
Neitzel Julia,
Franzmeier Nicolai,
Rubinski Anna,
Binette Alexa Pichet,
Poirier Judes,
Villeneuve Sylvia,
Ewers Michael
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.046206
Subject(s) - apolipoprotein e , dementia , amyloid (mycology) , medicine , longitudinal study , oncology , psychology , alzheimer's disease neuroimaging initiative , cohort , neuroscience , pathology , disease
Background ApoE4 carriage is the strongest genetic risk factor for developing late‐onset AD. Previous studies suggest that ApoE is involved in the amyloid pathway, and that elevated AD risk in ApoE4‐carriers is conferred by higher beta‐amyloid levels. However, recent animal work suggests that ApoE4 is also associated with increased tau pathology (Shi et al, 2017, Nature). Yet, it is unclear whether this association between ApoE4 and tau pathology translates to humans. Thus, the main aim of the current study was to test whether ApoE4 has an amyloid‐independent effect on cross‐sectional and longitudinal tau‐PET in humans. Method For longitudinal analyses, we included baseline AV45 amyloid‐PET and longitudinal AV1451 tau‐PET (∼1.3 years follow‐up) from 111 ADNI participants (42ε4+,69ε4‐) including cognitively normal (CN), mild cognitive impairment (MCI) and AD dementia (ADD). For cross‐sectional analyses, we additionally included tau‐ and amyloid‐PET from 254 CN and MCI participants (83ε4+,171ε4) from ADNI (not overlapping with the longitudinal ADNI sample) plus 128 CN participants (53ε4+,75ε4‐) from the PREVENT‐AD cohort (Table 1). Average baseline PET‐SUVR and annual change rates were quantified within 68 Freesurfer‐defined cortical brain regions (Figure 1). Analysis of covariance (ANCOVA) was used to investigate differences in cross‐sectional tau‐PET or longitudinal tau‐PET changes between ApoE4 carriers versus non‐carriers, controlling continuous measures of global amyloid‐PET. Post‐hoc subgroup analyses tested potential ApoE4 effects with a more rigorous control of amyloid‐PET by including only participants with the same amyloid status. Result For cross‐sectional analyses, we found ApoE4 carriers to show higher tau‐PET compared to non‐carriers after controlling global amyloid‐PET (Figure 2). Across samples, medial temporal areas (entorhinal cortex,parahippocampus) showed the strongest ApoE effect. The amyloid‐independent effect of ApoE4 on medial temporal tau‐PET remained significant in post‐hoc analyses of only amyloid‐positive ADNI or amyloid‐negative PREVENT‐AD participants (data not shown). For longitudinal analyses, we found significantly higher tau‐PET changes in ApoE4 carriers controlled for baseline amyloid‐PET (Figure 3). Strongest effects were found in posterior brain areas (lateral occipital, superior parietal) which remained significant in post‐hoc subgroup analyses. Conclusion The current results suggest that there is an amyloid‐independent association between ApoE4 and elevated tau‐PET specifically in medial temporal regions.