Affiliations: [a] Department of Neurology, Fundación Jiménez Díaz, Madrid, Spain
| [b] Department of Immunology, Fundación Jiménez Díaz, Madrid, Spain
| [c] Department of Genetics, Fundación Jiménez Díaz, Madrid, Spain
| [d] Department of Neurology, Hospital Ramón y Cajal, Madrid, Spain
| [e] Department of Nuclear Medicine, Hospital Ramón y Cajal, Madrid, Spain
Correspondence:
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Correspondence to: Dr. Estrella Gómez-Tortosa, Department of Neurology, Fundación Jiménez Díaz, Avenida de los Reyes Católicos 2, 28040 Madrid, Spain. Tel.: +34 91 5504800 ext. 2063; E-mail: [email protected].
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, presenilin 1 mutation, posterior cortical atrophy
