APOε2 and education in cognitively normal older subjects with high levels of AD pathology at autopsy: Findings from the Nun Study

Diego Iacono, Peter Zandi, Myron Gross, William R. Markesbery, Olga Pletnikova, Gay Rudow, Juan C. Troncoso

Research output: Contribution to journalArticlepeer-review

Abstract

Asymptomatic Alzheimer's disease (ASYMAD) subjects are individuals characterized by preserved cognition before death despite substantial AD pathology at autopsy. ASYMAD subjects show comparable levels of AD pathology, i.e. β-amyloid neuritic plaques (Aβ-NP) and tau-neurofibrillary tangles (NFT), to those observed in mild cognitive impairment (MCI) and some definite AD cases. Previous clinicopathologic studies on ASYMAD subjects have shown specific phenomena of hypertrophy in the cell bodies, nuclei, and nucleoli of hippocampal pyramidal neurons and other cerebral areas. Since it is well established that the allele APOε4 is a major genetic risk factor for AD, we examined whether specific alleles of APOE could be associated with the different clinical outcomes between ASYMAD and MCI subjects despite equivalent AD pathology. A total of 523 brains from the Nun Study were screened for this investigation. The results showed higher APOε2 frequency (p < 0.001) in ASYMAD (19.2%) vs. MCI (0%) and vs. AD (4.7%). Furthermore, higher education in ASYMAD vs. MCI and AD (p < 0.05) was found. These novel autopsy-verified findings support the hypothesis of the beneficial effect of APOε2 and education, both which seem to act as contributing factors in delaying or forestalling the clinical manifestations of AD despite consistent levels of AD pathology.

Original languageEnglish (US)
Pages (from-to)14082-14091
Number of pages10
JournalOncotarget
Volume6
Issue number16
DOIs
StatePublished - 2015

Keywords

  • AD pathology
  • APOε2
  • Higher education and language skills
  • Neuronal hypertrophy
  • Preserved cognition

ASJC Scopus subject areas

  • Oncology

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