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P4‐058: VASCULAR CONTRIBUTIONS TO ALZHEIMER'S DISEASE: A SYSTEMS PHYSIOLOGY PERSPECTIVE
Author(s) -
Kandimalla Karunya K.,
Swaminathan Suresh K.,
Sarma Vidur V.,
Curran Geoffry L.,
Bruinsma Tyler J.,
Decklever Teresa,
Min Hoon-Ki,
Kalari Krishna Rani,
Lowe Val J.
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.2461
Subject(s) - insulin resistance , insulin , hyperinsulinemia , blood–brain barrier , insulin receptor , endocrinology , medicine , biology , neuroscience , central nervous system
been previously reported that human apoE might play a role in the inflammatory response of cells. Since inflammation and neurodegeneration are closely linked, we aimed at analyzing the role of apoE in modulating the inflammatory response of isogenic astrocytes. Indeed, stimulating these astrocytes with a cytokine cocktail triggered a differential inflammatory response depending on the apoE genotype. ApoE4 carrying astrocytes displayed stronger pro-inflammatory responses compared to apoE3 cells indicating a potential role for neuro-inflammation in AD. In this study the analysis of these differences was extended to additional apoE genotypes, like apoE2/2 and also included the heterozygote form apoE3/4. ApoE has also been reported to influence the complexity of neuronal networks denoted by the neuron’s ability to grow and extend neurites. However, this has not been tested in humanderived cells. Therefore, we investigated the impact of the various apoE isoforms on the differentiation and maturation of cortical neurons under basal conditions and in the presence of various stressors. Conclusions:Since apoE4 is a significant factor in the development of late onset AD, we believe that our mechanistic studies help understand its role in the disease course, and ultimately bring us closer to developing impactful treatments.