@misc{10481/61302,
year = {2020},
url = {http://hdl.handle.net/10481/61302},
abstract = {Background: Diabetes is a risk factor for developing Alzheimer’s disease (AD); however, the mechanism by which
diabetes can promote AD pathology remains unknown. Diabetes results in diverse molecular changes in the brain,
including dysregulation of glucose metabolism and loss of cerebrovascular homeostasis. Although these changes
have been associated with increased Aβ pathology and increased expression of glial activation markers in APPswe/
PS1dE9 (APP/PS1) mice, there has been limited characterization, to date, of the neuroinflammatory changes
associated with diabetic conditions. Results: Our analysis revealed that pathology associated with either db/db, HFD, or STZ models yielded
upregulation of a broad profile of cytokines, including chemokines (e.g., MIP-1α, MIP-1β, and MCP-1) and proinflammatory
cytokines, including IL-1α, IFN-γ, and IL-3. Moreover, multivariate partial least squares regression
analysis showed that combined diabetic-APP/PS1 models yielded cooperatively enhanced expression of the
cytokine profile associated with each diabetic model alone. Finally, in APP/PS1xdb/db mice, we found that
circulating levels of Aβ1-40, Aβ1-42, glucose, and insulin all correlated with cytokine expression in the brain,
suggesting a strong relationship between peripheral changes and brain pathology.
Conclusions: Altogether, our multiplexed analysis of cytokines shows that Alzheimer’s and diabetic pathologies
cooperate to enhance profiles of cytokines reported to be involved in both diseases. Moreover, since many of the
identified cytokines promote neuronal injury, Aβ and tau pathology, and breakdown of the blood-brain barrier, our
data suggest that neuroinflammation may mediate the effects of diabetes on AD pathogenesis. Therefore, strategies
targeting neuroinflammatory signaling, as well as metabolic control, may provide a promising strategy for
intervening in the development of diabetes-associated AD.},
organization = {This work was funded in part by Programa Estatal de I+D+I orientada a los
Retos de la Sociedad (BFU 2016-75038-R), financed by the Agencia Estatal de
Investigación (AEI) and the Fondo Europeo de Desarrollo Regional (FEDER),
Ministerio de Ciencia, Innovación y Universidades, Explora Ciencia, Ministerio
de Ciencia, Innovación y Universidades (BFU2017-91910-EXP), Subvención
para la financiación de la investigación y la innovación biomédica y en ciencias
de la salud en el marco de la Iniciativa Territorial Integrada 2014–2020
para la provincia de Cádiz, Consejeria de Salud, Junta de Andalucia, Union
Europea, financed by the Fondo de Desarrollo Regional (FEDER) (PI-0008-
2017) (M.G.A.). This work was also supported by startup funds from the
George W. Woodruff School of Mechanical Engineering at Georgia Tech
(L.B.W.) and by the National Institutes of Health under grant number R33
ES025661 04S1. LDW was supported in part by the National Institutes of Health Cell and Tissue Engineering Biotechnology Training Grant (T32-
GM008433).},
publisher = {Springer Nature},
keywords = {Pre-diabetes},
keywords = {Type 1 diabetes (T1D)},
keywords = {Type 2 diabetes (T2D)},
keywords = {Cytokine profile},
title = {Amyloid beta and diabetic pathology cooperatively stimulate cytokine expression in an Alzheimer’s mouse model},
doi = {10.1186/s12974-020-1707-x},
author = {Sankar, Sitara B. and Ramos Rodríguez, Juan José},
}