Apolipoprotein epsilon 3 alleles are associated with indicators of neuronal resilience

BMC Medicine

Research Article

Frederick Boop¹  Robert E Mrak²  Orwa Aboud³  Sue T Griffin⁴ 

[1]Department of Neurosurgery, University of Tennessee Health Sciences Center, 50 N Dunlap St, 38163, Memphis, TN, USA

[2]Department of Pathology, University of Toledo Health Sciences Campus, 3000 Arlington Avenue, 43614, Toledo, OH, USA

[3]Donald W. Reynolds Department of Geriatrics, Reynolds Institute on Aging, 629 Jack Stephens Drive, 72205, Little Rock, AR, USA

[4]Department of Neurobiology and Developmental Sciences, University of Arkansas College of Medicine, 4300 Markham Street, 72205, Little Rock, AR, USA

[5]Donald W. Reynolds Department of Geriatrics, Reynolds Institute on Aging, 629 Jack Stephens Drive, 72205, Little Rock, AR, USA

[6]Geriatric Research Education Clinical Center, Central Arkansas Veterans Healthcare Systems, 4300 West Seventh Street, 72205, Little Rock, AR, USA

[7]Department of Neurobiology and Developmental Sciences, University of Arkansas College of Medicine, 4300 Markham Street, 72205, Little Rock, AR, USA

关键词: Amyloid beta (Aβ);    Alzheimer disease;    APOE;    DNA damage;    epilepsy;    interleukin-1;    neuroinflammation;    phosphorylated tau;    synaptophysin;    TUNEL;   

DOI  :  10.1186/1741-7015-10-35

 received in 2011-12-11, accepted in 2012-04-13,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundEpilepsy is associated with precocious development of Alzheimer-type neuropathological changes, including appearance of senile plaques, neuronal loss and glial activation. As inheritance of APOE ε4 allele(s) is reported to favor this outcome, we sought to investigate neuronal and glial responses that differ according to APOE genotype. With an eye toward defining ways in which APOE ε3 alleles may foster neuronal well-being in epilepsy and/or APOE ε4 alleles exacerbate neuronal decline, neuronal and glial characteristics were studied in temporal lobectomy specimens from epilepsy patients of either APOE ε4,4 or APOE ε3,3 genotype.MethodsTissue and/or cellular expressions of interleukin-1 alpha (IL-1α), apolipoprotein E (ApoE), amyloid β (Aβ) precursor protein (βAPP), synaptophysin, phosphorylated tau, and Aβ were determined in frozen and paraffin-embedded tissues from 52 APOE ε3,3 and 7 APOE ε4,4 (0.25 to 71 years) epilepsy patients, and 5 neurologically normal patients using Western blot, RT-PCR, and fluorescence immunohistochemistry.ResultsTissue levels of IL-1α were elevated in patients of both APOE ε3,3 and APOE ε4,4 genotypes, and this elevation was apparent as an increase in the number of activated microglia per neuron (APOE ε3,3 vs APOE ε4,4 = 3.7 ± 1.2 vs 1.5 ± 0.4; P < 0.05). This, together with increases in βAPP and ApoE, was associated with apparent neuronal sparing in that APOE ε4,4 genotype was associated with smaller neuron size (APOE ε4,4 vs APOE ε3,3 = 173 ± 27 vs 356 ± 45; P ≤ 0.01) and greater DNA damage (APOE ε4,4 vs APOE ε3,3 = 67 ± 10 vs 39 ± 2; P = 0.01). 3) Aβ plaques were noted at early ages in our epilepsy patients, regardless of APOE genotype (APOE ε4,4 age 10; APOE ε3,3 age 17).ConclusionsOur findings of neuronal and glial events, which correlate with lesser neuronal DNA damage and larger, more robust neurons in epilepsy patients of APOE ε3,3 genotype compared to APOE ε4,4 genotype carriers, are consistent with the idea that the APOE ε3,3 genotype better protects neurons subjected to the hyperexcitability of epilepsy and thus confers less risk of AD (Alzheimer's disease).Please see related article: http://www.biomedcentral.com/1741-7015/10/36

【 授权许可】

Unknown   
© Aboud et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.