Diagnostic Approach of Early-Onset Dementia with Negative Family History: Implications from Two Cases of Early-Onset Alzheimer's Disease with De Novo PSEN1 Mutation

J Alzheimers Dis. 2019;68(2):551-558. doi: 10.3233/JAD-181108.


For early-onset Alzheimer's disease (EOAD) cases with unclear family history, most cases are sporadic. Some cases are positive in genetic findings, that is, either incomplete penetrance or de novo mutation. We aimed to focus on EOAD cases with de novo mutations. Case reports and literature review were performed. The implication for diagnostic approach of early-onset dementia with negative family history was developed. We reported two Chinese EOAD cases with de novo mutations. The genotype PSEN1 G206S appeared to correlate with the phenotype of EOAD with pure cognitive problems. The second case had a PSEN1 M233V mutation with an earlier age of onset of 25 with cognitive decline, parkinsonism, and epilepsy. Although EOAD due to de novo mutations is not common, it should be considered in patients with a phenotype of progressive cognitive decline and amyloid positivity on PET or CSF analysis.

Keywords: De novo PSEN1 mutation; diagnostic approach; early-onset Alzheimer’s disease; early-onset dementia with negative family history.

Publication types

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

MeSH terms

  • Adult
  • Age of Onset
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / genetics*
  • Brain / diagnostic imaging
  • Diagnosis, Differential
  • Epilepsy / diagnosis
  • Epilepsy / genetics
  • Humans
  • Male
  • Mutation*
  • Parkinsonian Disorders / diagnosis
  • Parkinsonian Disorders / genetics
  • Phenotype
  • Presenilin-1 / genetics*


  • PSEN1 protein, human
  • Presenilin-1