APOE2 is associated with amyloid independent effects on tau PET signal in preclinical AD. (20th December 2022)

• Record Type: Journal Article
• Authors: Young, Christina B; Kennedy, Gabriel; Sperling, Reisa A.; Buckley, Rachel F.; Insel, Philip S.; Greicius, Michael D; Poston, Kathleen L; Mormino, Elizabeth C.
• Is Part Of: Alzheimer's & dementia. Volume 18(2022)Supplement 6
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-20
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.064009
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Although APOE is strongly associated with risk of amyloid‐positivity during the preclinical stage of AD, less is known regarding independent effects on regional tau PET burden. Method: We examined 385 Amyloid‐positive (A+) clinically unimpaired (CU) individuals that had APOE genotype available and additionally underwent amyloid (florbetapir) and tau (flortaucipir) PET imaging as part of the A4‐LEARN study (Table 1A, mean age=72.1±4.8). PET data were processed locally using FreeSurfer defined regions to quantify regional tau and combined to form a large cortical target composite for amyloid. Multiple regression was used to examine associations between APOE genotype (number of e2 and number of e4 modeled as two predictors) with global amyloid, regional tau (entorhinal, amygdala, and inferior temporal). Result: Among the A+ group, each APOE2 allele was associated with a decrease of 0.045 SUVR while each APOE4 allele was associated with an increase of 0.068 SUVR units of global amyloid compared to the APOE3/3 group (Table 1B ). APOE2 was significantly associated with reduced tau across medial temporal lobe ROIs whereas APOE4 was associated with elevated tau in the medial temporal lobe ROIs (Table 1B, Figure 1 ). Although continuous amyloid levels were associated both with APOE genotype, the total effect of both APOE2 and APOE4 dosage on tau PET was largely independent of continuous amyloid levels (Figure 2 ). Conclusion: APOE genotype is related to early medial temporal lobe tau burden, independent of continuous amyloid burden within the A+ range. These findings highlight that APOE genotype influences heterogeneity in tau burden among individuals with preclinical AD.