Apolipoprotein epsilon 3 alleles are associated with indicators of neuronal resilience

作者：Aboud Orwa; Mrak Robert E; Boop Frederick; Griffin Sue T^*

来源：BMC Medicine, 2012, 10: 35.

DOI：10.1186/1741-7015-10-35

• Amyloid beta (A beta?beta?)
• Alzheimer disease
• APOE genotype
• DNA damage
• epilepsy
• interleukin-1
• neuroinflammation
• phosphorylated tau
• synaptophysin
• TUNEL

Background: Epilepsy is associated with precocious development of Alzheimer-type neuropathological changes, including appearance of senile plaques, neuronal loss and glial activation. As inheritance of APOE epsilon 4 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 epsilon 3 alleles may foster neuronal well-being in epilepsy and/or APOE epsilon 4 alleles exacerbate neuronal decline, neuronal and glial characteristics were studied in temporal lobectomy specimens from epilepsy patients of either APOE epsilon 4,4 or APOE epsilon 3,3 genotype. %26lt;br%26gt;Methods: Tissue and/or cellular expressions of interleukin-1 alpha (IL-1 alpha), apolipoprotein E (ApoE), amyloid beta (A beta) precursor protein (beta APP), synaptophysin, phosphorylated tau, and A beta were determined in frozen and paraffin-embedded tissues from 52 APOE epsilon 3,3 and 7 APOE epsilon 4,4 (0.25 to 71 years) epilepsy patients, and 5 neurologically normal patients using Western blot, RT-PCR, and fluorescence immunohistochemistry. %26lt;br%26gt;Results: Tissue levels of IL-1 alpha were elevated in patients of both APOE epsilon 3,3 and APOE epsilon 4,4 genotypes, and this elevation was apparent as an increase in the number of activated microglia per neuron (APOE epsilon 3,3 vs APOE epsilon 4,4 = 3.7 +/- 1.2 vs 1.5 +/- 0.4; P %26lt; 0.05). This, together with increases in beta APP and ApoE, was associated with apparent neuronal sparing in that APOE epsilon 4,4 genotype was associated with smaller neuron size (APOE epsilon 4,4 vs APOE epsilon 3,3 = 173 +/- 27 vs 356 +/- 45; P %26lt;= 0.01) and greater DNA damage (APOE epsilon 4,4 vs APOE epsilon 3,3 = 67 +/- 10 vs 39 +/- 2; P = 0.01). 3) A beta plaques were noted at early ages in our epilepsy patients, regardless of APOE genotype (APOE epsilon 4,4 age 10; APOE epsilon 3,3 age 17). %26lt;br%26gt;Conclusions: Our findings of neuronal and glial events, which correlate with lesser neuronal DNA damage and larger, more robust neurons in epilepsy patients of APOE epsilon 3,3 genotype compared to APOE epsilon 4,4 genotype carriers, are consistent with the idea that the APOE epsilon 3,3 genotype better protects neurons subjected to the hyperexcitability of epilepsy and thus confers less risk of AD (Alzheimer%26apos;s disease). Please see related article: http://www.biomedcentral.com/1741-7015/10/36

• 出版日期2012-4-13