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Primary progressive aphasia: ReADing the clinical GRANularity.

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Primary progressive aphasia diagnosis is complex. Atypical features in logopenic aphasia, even with Alzheimer biomarkers, may indicate progranulin gene mutations, requiring careful clinical evaluation.

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Area of Science:

  • Neurology
  • Genetics
  • Neurodegenerative Diseases

Background:

  • Primary progressive aphasia (PPA) presents diagnostic challenges, complicated by numerous ancillary tests and biomarkers.
  • Logopenic aphasia (LPA) is one PPA subtype, often associated with Alzheimer's disease pathology.

Observation:

  • A 67-year-old man initially presented with sporadic LPA and positive Alzheimer biomarkers.
  • He exhibited atypical early symptoms including mild expressive agrammatism, behavioral changes, and rapid clinical decline.

Findings:

  • Genetic testing revealed a pathogenic mutation in the progranulin (GRN) gene.
  • This case highlights that LPA can co-occur with or be masked by other pathologies, such as GRN mutations.

Implications:

  • The diagnostic landscape of PPA requires integrating clinical nuances with biomarker data.
  • Recognizing atypical variants of PPA syndromes is crucial for identifying underlying genetic causes and alternative pathologies.
  • Careful clinical analysis remains paramount for accurate PPA diagnosis and guiding appropriate investigations.