Presenilin-1 C779T Mutation Presenting With Rapidly Progressive Dementia and Medial Temporal Lobe MRI Changes

Introduction: Autosomal dominant Alzheimer's disease (ADAD), especially due to presenilin-1 (PSEN-1) gene mutations, may display a broad spectrum of clinical manifestations and neuroradiological findings. Occasionally, these manifestations may be rare and atypical, challenging the clinician's ability to recognize the disease. The description of the clinical characteristics and neuroradiological remarks of patients with specific mutations may improve clinicians' ability to identify them.

Case presentation: We report the case of a woman who presented with early-onset, rapidly progressive dementia associated with bilateral hyperintensity of the medial temporal lobe on T2-weighted MRI. After more common etiologies were excluded, genetic testing revealed a PSEN-1 C779T mutation. Notably, her brother, who carried the same mutation, did not exhibit these atypical neuroradiological findings.

Conclusions: This case underscores the phenotypic variability associated with PSEN-1 mutations, even among individuals within the same family. Such variability and the possibility of atypical presentations may complicate the diagnostic process. In the presence of early-onset and rapidly progressive dementia associated with bilateral hyperintensity of the medial temporal lobe, ADAD and PSEN-1 mutation may be suspected and need to be addressed.