RT journal article
T1 Accelerated amyloid angiopathy and related vascular alterations in a mixed murine model of Alzheimer´s disease and type two diabetes
A1 Vargas Soria, María
A1 Ramos-Rodríguez, Juan José
A1 Marco Delgado, Ángel José del
A1 Hierro Bujalance, Carmen
A1 Carranza Naval,  María José
A1 Calvo-Rodriguez, Maria
A1 van Veluw, Susanne J.
A1 Stitt, Alan W.
A1 Simó, Rafael
A1 Bacskai, Brian J.
A1 Infante-Garcia, Carmen
A1 García Alloza, Mónica
A2 BiomedicinaBiotecnología y Salud Pública
K1 Alzheimer’s disease
K1 Type 2 diabetes
K1 Prediabetes
K1 Multiphoton microscopy
K1 Amyloid
K1 Oxidative stress
K1 Matrix metalloproteinases
AB Background While aging is the main risk factor for Alzheimer ' s disease (AD), emerging evidence suggests that metabolic alterations such as type 2 diabetes (T2D) are also major contributors. Indeed, several studies have described a close relationship between AD and T2D with clinical evidence showing that both diseases coexist. A hallmark pathological event in AD is amyloid-beta (A beta) deposition in the brain as either amyloid plaques or around leptomeningeal and cortical arterioles, thus constituting cerebral amyloid angiopathy (CAA). CAA is observed in 85-95% of autopsy cases with AD and it contributes to AD pathology by limiting perivascular drainage of A beta. Methods To further explore these alterations when AD and T2D coexist, we have used in vivo multiphoton microscopy to analyze over time the A beta deposition in the form of plaques and CAA in a relevant model of AD (APPswe/PS1dE9) combined with T2D (db/db). We have simultaneously assessed the effects of high-fat diet-induced prediabetes in AD mice. Since both plaques and CAA are implicated in oxidative-stress mediated vascular damage in the brain, as well as in the activation of matrix metalloproteinases (MMP), we have also analyzed oxidative stress by Amplex Red oxidation, MMP activity by DQ((TM)) Gelatin, and vascular functionality. Results We found that prediabetes accelerates amyloid plaque and CAA deposition, suggesting that initial metabolic alterations may directly affect AD pathology. T2D significantly affects vascular pathology and CAA deposition, which is increased in AD-T2D mice, suggesting that T2D favors vascular accumulation of A beta. Moreover, T2D synergistically contributes to increase CAA mediated oxidative stress and MMP activation, affecting red blood cell velocity. Conclusions Our data support the cross-talk between metabolic disease and A beta deposition that affects vascular integrity, ultimately contributing to AD pathology and related functional changes in the brain microvasculature.
PB BMC
SN 2045-8118
YR 2022
FD 2022-11
LK http://hdl.handle.net/10498/29546
UL http://hdl.handle.net/10498/29546
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 10-nov-2026