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Clinical Manifestations.

Hulya Ulugut1, Kyan Younes2, Maxime Bertoux3

  • 1Memory & Aging Center, Department of Neurology, University of California in San Francisco, San Francisco, CA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Summary
This summary is machine-generated.

Frontotemporal dementia (FTD) with right anterior temporal lobe atrophy often appears sporadic but has genetic variants. These subtypes show distinct pathology and clinical features, crucial for tailored treatments and clinical trials.

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Area of Science:

  • Neuroscience
  • Neurology
  • Genetics

Background:

  • Frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) atrophy is an emerging subtype of FTD.
  • International Working Group (IWG) findings highlight its distinct clinical profile.
  • Genetic and pathological factors in large, multicultural RATL-FTD cohorts remain understudied.

Purpose of the Study:

  • To investigate the genetic and pathological underpinnings of FTD with predominant RATL atrophy.
  • To analyze clinical, genetic, pathological, and neuroimaging data from a large, multicultural cohort.
  • To identify distinct features of sporadic versus genetic RATL-FTD subtypes.

Main Methods:

  • Retrospective analysis of data from 444 patients with RATL-FTD across 23 IWG sites in 13 countries.
  • Genetic screening for major frontotemporal lobar degeneration (FTLD) mutations (MAPT, GRN, C9orf72) and dementia panels in 51% of the cohort.
  • Pathological confirmation in 63 patients, categorizing findings into sporadic, genetic, or heterogeneous.

Main Results:

  • 81% of screened patients had sporadic FTD with negative genetic results.
  • Microtubule-associated protein tau (MAPT) mutations were the most common genetic variant (7% of screened).
  • Transactive response DNA-binding protein 43 type C (TDP-C) pathology was prevalent in sporadic cases (60%), while tau-MAPT pathology was common in genetic cases (38%). Patients with TDP-C pathology were older and more frequently had semantic deficits.

Conclusions:

  • FTD with RATL atrophy is predominantly sporadic but includes a significant genetic component.
  • Sporadic and genetic subtypes exhibit distinct neuropathological and clinical characteristics.
  • Precise clinical and molecular subtyping is essential for targeted therapeutic strategies and clinical trial enrollment.