Longitudinal trajectories of divergent cortical tau patterns in preclinical Alzheimer's disease - PubMed
3 hours ago
- #longitudinal trajectories
- #cortical tau patterns
- #preclinical Alzheimer's disease
- Approximately 10% of clinically unimpaired individuals with abnormal amyloid (preclinical Alzheimer's) show 'divergent' cortical tau patterns (A+TCortical+), defined as greater than expected cortical tau relative to medial temporal lobe and/or cortical asymmetry on tau PET.
- Longitudinal study of 395 clinically unimpaired participants (65-85 years) from the A4 Study, with 2-5 flortaucipir tau PET scans over ~4.7 years, comparing A+TCortical+ (n=34) to other biomarker groups: A+TMTL+ (elevated medial temporal lobe tau only, n=102), A+TMTL- (amyloid positive, no significant tau, n=210), and A-TMTL- (no amyloid or tau, n=49).
- Cortical tau accumulation was fastest in A+TCortical+ (0.018-0.034 SUVR/year), while medial temporal lobe tau accumulation was similar across A+TCortical+, A+TMTL+, and A+TMTL- groups (0.010-0.013 SUVR/year).
- Asymmetrical tau patterns at baseline in A+TCortical+ participants were maintained over time, with tau continuing to accumulate in affected regions and contralateral homotopic regions; younger A+TCortical+ participants showed especially fast cortical tau accumulation.
- A+TCortical+ group had significantly greater neurodegeneration and faster clinical decline (CDR-SB: 0.610 points/year; MMSE: -0.780 points/year) compared to other subgroups (CDR-SB: 0.048-0.182; MMSE: -0.189-0.006).
- Conclusion: Individuals with divergent cortical tau patterns are a small, high-risk subgroup in preclinical Alzheimer's, with faster cortical tau accumulation, greater neurodegeneration, and quicker cognitive/functional decline, potentially disproportionately influencing clinical trials and research if not subtyped.