Phenotypic Variability in Autosomal Dominant Familial Alzheimer Disease due to the S170F Mutation of Presenilin-1

Neurodegener Dis. 2018;18(2-3):57-68. doi: 10.1159/000485899. Epub 2018 Feb 22.


Background: In rare cases, patients with Alzheimer disease (AD) present at an early age and with a family history suggestive of an autosomal dominant mode of inheritance. Mutations of the presenilin-1 (PSEN1) gene are the most common causes of dementia in these patients. Early-onset and particularly familial AD patients frequently present with variable non-amnestic cognitive symptoms such as visual, language or behavioural changes as well as non-cognitive, e.g. motor, symptoms.

Objective: To investigate the phenotypic variability in carriers of the PSEN1 S170F mutation.

Methods: We report a family with 4 patients carrying the S170F mutation of whom 2 underwent detailed clinical examinations. We discuss our current findings in the context of previously reported S170F cases.

Results: The clinical phenotype was consistent regarding initial memory impairment and early onset in the late twenties found in all S170F patients. There were frequent non-amnestic cognitive changes and, at early stages of the disease, indications of a more pronounced disturbance of visuospatial abilities as compared to face and object recognition. Non-cognitive symptoms most often included myoclonus and cerebellar ataxia. A review of the available case reports indicates some phenotypic variability associated with the S170F mutation including different constellations of symptoms such as parkinsonism and delusions.

Conclusion: The variable clinical findings associated with the S170F mutation highlight the relevance of atypical phenotypes in the context of research and under a clinical perspective. CSF sampling and detection of Aβ species may be essential to indicate AD pathology in unclear cases presenting with cognitive and motor symptoms at a younger age.

Keywords: Alzheimer disease; Cerebellar ataxia; Early-onset Alzheimer disease; Familial Alzheimer disease; Hereditary diseases; Neurodegenerative disease; Neuropsychology; PSEN1 protein, human; Presenilin-1.

MeSH terms

  • Alzheimer Disease / genetics*
  • Amyloid beta-Protein Precursor / genetics*
  • Biological Variation, Population / genetics
  • Heterozygote
  • Humans
  • Male
  • Memory Disorders / genetics*
  • Middle Aged
  • Mutation / genetics*
  • Phenotype
  • Presenilin-1 / genetics*


  • Amyloid beta-Protein Precursor
  • Presenilin-1