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. 2015 Jun 10;6(16):14082-91.
doi: 10.18632/oncotarget.4118.

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

Diego Iacono  1   2   3   4 , Peter Zandi  5 , Myron Gross  6 , William R Markesbery  7   8   9 , Olga Pletnikova  1 , Gay Rudow  1 , Juan C Troncoso  1   10
Affiliations

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

Diego Iacono et al. Oncotarget. .

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.

Keywords: AD pathology; APOε2; Gerotarget; higher education and language skills; neuronal hypertrophy; preserved cognition.

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Conflict of interest statement

CONFLICTS OF INTEREST

Authors declare no conflicts of interests.

Figures

Figure 1
Figure 1. The figure shows histograms for the frequency distribution of APOε2, ε3, and ε4 alleles in the four different groups examined in the study
Figure 2
Figure 2. The figure shows the histograms for APOε2 frequencies and educational levels in two different groups: 1) preserved cognition group (PCG): controls+ASYMAD subjects; and 2) impaired cognition group (ICG): MCI+AD patients. The p-values are the statistical significance values after exact Fisher's test
See this image and copyright information in PMC

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