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

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.