Medial temporal lobe tau-neurodegeneration mismatch from structural imaging and plasma biomarkers.

In medial temporal lobe segments of amyloid-positive Alzheimer’s disease patients, MRI thickness versus plasma ptau217 identifies three T–N phenotypes, including a “vulnerable” group with N > T and faster cognitive decline.

• Why it matters: Tau and neurodegeneration can diverge, potentially reflecting non-Alzheimer’s disease co-pathologies. This work targets how medial temporal lobe mismatch relates to vulnerability versus resilience in cognitively impaired or unimpaired patients.
• What they did: The authors parcellated the medial temporal lobe into 100 contiguous segments, using plasma ptau217 for tau and thickness for neurodegeneration, then clustered 447 amyloid-positive individuals from ADNI into data-driven T–N phenotypes. They replicated the clustering in an independent cohort and applied the model to 50 lecanemab-treated patients.
• The result: The “vulnerable” phenotype showed anterior medial temporal lobe atrophy extending into temporal-limbic regions, neurodegeneration preceding estimated tau onset, and faster multi-domain cognitive decline, consistent with mixed LATE-NC with Alzheimer’s disease. The “canonical” (N ∼ T) and “resilient” (N < T) groups showed Alzheimer's-like or minimal atrophy and preserved cognition, respectively.

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