Clinical features and APOE genotype of pathologically proven early-onset Alzheimer disease

Neurology. 2011 May 17;76(20):1720-5. doi: 10.1212/WNL.0b013e31821a44dd.


Objectives: Early-onset Alzheimer disease (EOAD) diagnosis often represents a challenge because of the high frequency of atypical presentations. Our aim was to describe the clinical features, APOE genotype, and its pathologic correlations of neuropathologic confirmed EOAD.

Methods: Retrospective review of clinical data (age at onset, family history, clinical presentation, diagnostic delay, diagnosis) and APOE genotype of patients with neuropathologically confirmed EOAD (<60 years).

Results: Forty cases were selected. Mean age at onset was 54.5 years (range 46-60). The mean disease duration was 11 years with a mean diagnostic delay of 3.1 years. A total of 37.5% had a nonmemory presentation. Behavioral/executive dysfunction was the most prevalent atypical presentation. Incorrect initial clinical diagnoses were common (53%) in patients with atypical presentations, but rare when anterograde amnesia was the presenting symptom (4%). The incorrect initial clinical diagnoses were 2 behavioral variant frontotemporal lobar degeneration, 2 normal pressure hydrocephalus, 1 semantic dementia, 1 primary progressive aphasia, 1 corticobasal degeneration, 1 pseudodementia with depression, and 1 unclassifiable dementia. APOE genotype was ε3/ε3 in 59%, with no significant differences between typical and atypical presentations. APOE ε4 was 3.3 times more frequent in subjects with family history of AD. A total of 97.5% of the cases presented advanced neurofibrillary pathology. A total of 45% of the patients had concomitant Lewy body pathology although localized in most cases and without a significant clinical correlate.

Conclusion: One third of patients with pathologic confirmed EOAD presented with atypical symptoms. Patients with EOAD with nonamnestic presentations often receive incorrect clinical diagnoses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology*
  • Amyloid beta-Protein Precursor / genetics
  • Apolipoproteins E / genetics*
  • Autopsy
  • Brain / pathology
  • Cognition / physiology
  • DNA / genetics
  • Delayed Diagnosis
  • Female
  • Genotype
  • Humans
  • Lewy Bodies / pathology
  • Male
  • Memory Disorders / psychology
  • Middle Aged
  • Phenotype
  • Presenilin-1 / genetics
  • Presenilin-2 / genetics
  • Retrospective Studies
  • Tissue Banks


  • Amyloid beta-Protein Precursor
  • Apolipoproteins E
  • PSEN1 protein, human
  • PSEN2 protein, human
  • Presenilin-1
  • Presenilin-2
  • DNA