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Clinical Manifestations.

Gil D Rabinovici1, Renaud La Joie2

  • 1Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco (UCSF), San Francisco, CA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
PubMed
Summary

This study explores atypical Alzheimer's disease (AD) variants, focusing on clinical progression and challenges. Harmonizing data from multi-center studies like LEADS enhances understanding for targeted therapies.

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Area of Science:

  • Neuroscience
  • Clinical Neurology
  • Biomedical Research

Background:

  • Atypical Alzheimer's disease (AD) variants present unique challenges due to heterogeneity and earlier onset.
  • Unicentric cohorts provided initial insights into Posterior Cortical Atrophy (PCA) and logopenic Primary Progressive Aphasia (lvPPA) natural history.
  • Limited sample sizes in early studies necessitated larger, multi-center initiatives.

Purpose of the Study:

  • To examine the clinical progression of atypical AD variants.
  • To characterize disease trajectories for syndrome-specific clinical trials.
  • To harmonize clinical and neuroimaging datasets across multiple centers.

Main Methods:

  • Leveraging data from large, multi-center initiatives like the LEADS study.
  • Standardizing protocols for cognitive assessments, neuroimaging, and biomarker collection.
  • Integrating data from diverse cohorts to overcome rarity and variability challenges.

Main Results:

  • Harmonization efforts aim to create large, syndrome-specific cohorts for robust analysis.
  • Standardized protocols ensure consistency and comparability of data across sites.
  • Integrated data enhances statistical power for studying atypical AD progression.

Conclusions:

  • Standardized data harmonization is crucial for advancing research in atypical AD.
  • These efforts facilitate the development of innovative, tailored therapeutic strategies.
  • Improved understanding of atypical AD variants will ultimately enhance clinical outcomes.