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TAU AND HIPPOCAMPAL VOLUME REFLECT DISTINCT PROCESSES IN PRECLINICAL ALZHEIMER’S DISEASE

      Background

      To explore Tau and hippocampal volume as a function of age and beta-amyloid, as well as the contributions of these biomarkers to memory among older clinically normal (CN) participants.

      Methods

      We examined 143 CN participants from the Harvard Aging Brain Study that underwent PIB/AV1451 PET, structural MRI, and neuropsychological testing (mean age=75.5±6.9, age range=55-90). Effects related to age and Aβ status were compared for Tau in entorhinal cortex (EC) and inferior temporal (IT), as well as hippocampal volume. Hierarchical regression and path analysis was used to assess associations among Aβ, Tau, hippocampal volume, age, and cross-sectional memory performance.

      Results

      Age was related to hippocampal volume, regardless of Aβ status (within Aβ-: r= -0.63; within Aβ+: r= -0.52) (Figure 1A). Aβ+ showed significantly higher Tau than Aβ- in both EC (r= 0.44) and IT (r= 0.42); age was related to Tau in Aβ- (EC: r=0.32, IT: r= 0.35) but not within Aβ+ (EC: r=0.07, IT: r= 0.04)(Figure 1B-C). Although Tau was related to hippocampal volume among Aβ+ (EC: r= -0.28, IT: r= -0.29), the strength of these relationships were smaller than the association between age and hippocampal volume in Aβ+ (r= -0.52). Among Aβ-, 5.3% of the total variance in memory was explained by age, EC Tau, IT Tau, and hippocampal volume, with age accounting for the most unique variance (ΔR2= 1.7%). Among Aβ+, 32.5% of the total variance in memory was explained by age, EC Tau, IT Tau, and hippocampal volume, with IT Tau accounting for the most unique variance (ΔR2= 17.8%). Path analysis provided support for a model in which both EC and IT Tau are related to Aβ whereas hippocampal volume is related to age. Furthermore, EC Tau is more proximal to Aβ and IT Tau is more proximal to memory (Figure 2).

      Conclusions

      These results suggest that hippocampal volume largely reflects non-Aβ age-related etiologies whereas Tau is more specific for early AD processes during the asymptomatic stage of AD. Our results are consistent with a model by which Aβ exacerbates Tau in entorhinal cortex and catalyzes the spread of Tau into adjacent neocortex, which subsequently results in subtle memory impairment.
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