A novel presenilin1 mutation (Q223R) associated with early onset Alzheimer's disease, dysarthria and spastic paraparesis and decreased Abeta levels in CSF

Background and purpose:  A novel presenilin1 (PSEN1) mutation associated with dementia and spastic paraplegia in a family with five affected individuals is described. The index patient was a 35-year-old man presenting with cognitive decline, behavioural symptoms, dysarthria, and gait disorder due to spasticity. Methods and results:  Genetic analysis revealed a missense mutation Gln223Arg in exon 7. Initial CSF analysis revealed drastically decreased Abeta42 level despite marginally decreased FDG metabolism. Conclusion:  Cerebrospinal fluid biomarker analysis might point towards genetic analysis of PSEN1 in patients with positive family history and age of onset below 60 years.