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Alzheimer's Imaging Consortium.

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Summary
This summary is machine-generated.

In preclinical Alzheimer's disease (AD), tau PET scans reveal that tau accumulation is present in a subset of cognitively unimpaired individuals, with higher levels in those with mild cognitive impairment. These findings align with previous studies on tau deposition patterns in AD.

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Area of Science:

  • Neurology
  • Radiology
  • Gerontology

Background:

  • Preclinical Alzheimer's disease (AD) is characterized by amyloid buildup but often without cognitive impairment.
  • Previous trials indicate a low prevalence of elevated global tau in preclinical AD.
  • The TRAILBLAZER-ALZ 3 trial investigates donanemab efficacy in preclinical AD, necessitating baseline tau characterization.

Purpose of the Study:

  • To characterize and compare baseline tau positron emission tomography (PET) scans in the TRAILBLAZER-ALZ 3 trial.
  • To compare tau PET findings with those from the A4 and TRAILBLAZER-ALZ 2 studies.
  • To assess tau burden and regional patterns in preclinical AD populations.

Main Methods:

  • Analysis of baseline tau PET scans (flortaucipir F 18) from 310 participants in the TRAILBLAZER-ALZ 3 trial.
  • Participants were categorized by Clinical Dementia Rating-Global Score (CDR-GS 0 and CDR-GS 0.5).
  • Global tau burden was quantified using standardized uptake value ratio (SUVR) with established cut points; regional tau patterns were assessed using staging schemes.

Main Results:

  • 13.3% of CDR0 and 25.5% of CDR0.5 participants showed positive tau PET scans (SUVR > 1.11).
  • Both subgroups exhibited highest regional SUVRs in the medial and lateral temporal lobes.
  • Mean regional SUVRs were higher in the CDR0.5 subgroup compared to the CDR0 subgroup.

Conclusions:

  • Baseline tau PET patterns in TRAILBLAZER-ALZ 3 are consistent with other preclinical AD populations, including the CDR0.5 subgroup.
  • Findings support a sequential pattern of tau deposition: medial temporal, lateral temporal, parietal, and frontal lobes.
  • Further regional analyses are warranted to fully elucidate tau distribution in preclinical AD.