De Novo PS1 Mutation (Pro436Gln) in a Very Early-Onset Posterior Variant of Alzheimer's Disease Associated with Spasticity: A Case Report

J Alzheimers Dis. 2021;83(3):1011-1016. doi: 10.3233/JAD-210420.

Abstract

We report a patient with sporadic Alzheimer's disease with onset in his twenties found to carry the de novo Pro436Gln mutation in the presenilin 1 gene (PS1). Clinical phenotype featured a posterior cortical syndrome with severe visual agnosia and mild limb spasticity with brisk reflexes. Brain MRI and FDG-PET scans revealed severe parieto-occipital atrophy/hypometabolism. Cerebrospinal fluid biomarkers showed a decrease in Aβ42 level and Aβ42/40 ratio, increased phospho-tau, and normal total tau. Amyloid PET identified a very high burden of amyloid-β neuritic plaques in the posterior cortex. Similarities between this and two previously reported cases with this variant support that this mutation has a very strong impact on the clinical phenotype and is consistently associated with spasticity.

Keywords: Alzheimer’s disease; de novo mutation; early-onset dementia; posterior cortical atrophy; presenilin 1 mutation.

Publication types

  • Case Reports
  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Agnosia / etiology
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Muscle Spasticity / etiology*
  • Mutation*
  • Peptide Fragments / cerebrospinal fluid
  • Positron-Emission Tomography
  • Presenilin-1 / genetics*
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • PSEN1 protein, human
  • Peptide Fragments
  • Presenilin-1
  • amyloid beta-protein (1-42)
  • tau Proteins