Type 2 Diabetes Mellitus Increases the Risk of Late-Onset Alzheimer’s Disease: Ultrastructural Remodeling of the Neurovascular Unit and Diabetic Gliopathy

Type 2 diabetes mellitus (T2DM) and late-onset Alzheimer’s disease−dementia (LOAD) are increasing in global prevalence and current predictions indicate they will only increase over the coming decades. These increases may be a result of the concurrent increases of obesity and agin...

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Main Author: Melvin R. Hayden
Format: Article
Language:English
Published: MDPI AG 2019-09-01
Series:Brain Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3425/9/10/262
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spelling doaj-935fb1de07954a4f8aebff781a93dd942020-11-25T01:42:14ZengMDPI AGBrain Sciences2076-34252019-09-0191026210.3390/brainsci9100262brainsci9100262Type 2 Diabetes Mellitus Increases the Risk of Late-Onset Alzheimer’s Disease: Ultrastructural Remodeling of the Neurovascular Unit and Diabetic GliopathyMelvin R. Hayden0Diabetes and Cardiovascular Center, University of Missouri School of Medicine, Columbia, MO 65212, USAType 2 diabetes mellitus (T2DM) and late-onset Alzheimer&#8217;s disease&#8722;dementia (LOAD) are increasing in global prevalence and current predictions indicate they will only increase over the coming decades. These increases may be a result of the concurrent increases of obesity and aging. T2DM is associated with cognitive impairments and metabolic factors, which increase the cellular vulnerability to develop an increased risk of age-related LOAD. This review addresses possible mechanisms due to obesity, aging, multiple intersections between T2DM and LOAD and mechanisms for the continuum of progression. Multiple ultrastructural images in female diabetic <i>db/db</i> models are utilized to demonstrate marked cellular remodeling changes of mural and glia cells and provide for the discussion of functional changes in T2DM. Throughout this review multiple endeavors to demonstrate how T2DM increases the vulnerability of the brain&#8217;s neurovascular unit (NVU), neuroglia and neurons are presented. Five major intersecting links are considered: i. Aging (chronic age-related diseases); ii. metabolic (hyperglycemia advanced glycation end products and its receptor (AGE/RAGE) interactions and hyperinsulinemia-insulin resistance (a linking linchpin); iii. oxidative stress (reactive oxygen&#8722;nitrogen species); iv. inflammation (peripheral macrophage and central brain microglia); v. vascular (macrovascular accelerated atherosclerosis&#8212;vascular stiffening and microvascular NVU/neuroglial remodeling) with resulting impaired cerebral blood flow.https://www.mdpi.com/2076-3425/9/10/262agingalzheimer’s diseasebrain insulin resistance<i>db/db</i> diabetic mouse modeldiabetic cognopathyinsulin resistancemetabolic syndromemixed dementiaobesitytype 2 diabetes mellitus
collection DOAJ
language English
format Article
sources DOAJ
author Melvin R. Hayden
spellingShingle Melvin R. Hayden
Type 2 Diabetes Mellitus Increases the Risk of Late-Onset Alzheimer’s Disease: Ultrastructural Remodeling of the Neurovascular Unit and Diabetic Gliopathy
Brain Sciences
aging
alzheimer’s disease
brain insulin resistance
<i>db/db</i> diabetic mouse model
diabetic cognopathy
insulin resistance
metabolic syndrome
mixed dementia
obesity
type 2 diabetes mellitus
author_facet Melvin R. Hayden
author_sort Melvin R. Hayden
title Type 2 Diabetes Mellitus Increases the Risk of Late-Onset Alzheimer’s Disease: Ultrastructural Remodeling of the Neurovascular Unit and Diabetic Gliopathy
title_short Type 2 Diabetes Mellitus Increases the Risk of Late-Onset Alzheimer’s Disease: Ultrastructural Remodeling of the Neurovascular Unit and Diabetic Gliopathy
title_full Type 2 Diabetes Mellitus Increases the Risk of Late-Onset Alzheimer’s Disease: Ultrastructural Remodeling of the Neurovascular Unit and Diabetic Gliopathy
title_fullStr Type 2 Diabetes Mellitus Increases the Risk of Late-Onset Alzheimer’s Disease: Ultrastructural Remodeling of the Neurovascular Unit and Diabetic Gliopathy
title_full_unstemmed Type 2 Diabetes Mellitus Increases the Risk of Late-Onset Alzheimer’s Disease: Ultrastructural Remodeling of the Neurovascular Unit and Diabetic Gliopathy
title_sort type 2 diabetes mellitus increases the risk of late-onset alzheimer’s disease: ultrastructural remodeling of the neurovascular unit and diabetic gliopathy
publisher MDPI AG
series Brain Sciences
issn 2076-3425
publishDate 2019-09-01
description Type 2 diabetes mellitus (T2DM) and late-onset Alzheimer&#8217;s disease&#8722;dementia (LOAD) are increasing in global prevalence and current predictions indicate they will only increase over the coming decades. These increases may be a result of the concurrent increases of obesity and aging. T2DM is associated with cognitive impairments and metabolic factors, which increase the cellular vulnerability to develop an increased risk of age-related LOAD. This review addresses possible mechanisms due to obesity, aging, multiple intersections between T2DM and LOAD and mechanisms for the continuum of progression. Multiple ultrastructural images in female diabetic <i>db/db</i> models are utilized to demonstrate marked cellular remodeling changes of mural and glia cells and provide for the discussion of functional changes in T2DM. Throughout this review multiple endeavors to demonstrate how T2DM increases the vulnerability of the brain&#8217;s neurovascular unit (NVU), neuroglia and neurons are presented. Five major intersecting links are considered: i. Aging (chronic age-related diseases); ii. metabolic (hyperglycemia advanced glycation end products and its receptor (AGE/RAGE) interactions and hyperinsulinemia-insulin resistance (a linking linchpin); iii. oxidative stress (reactive oxygen&#8722;nitrogen species); iv. inflammation (peripheral macrophage and central brain microglia); v. vascular (macrovascular accelerated atherosclerosis&#8212;vascular stiffening and microvascular NVU/neuroglial remodeling) with resulting impaired cerebral blood flow.
topic aging
alzheimer’s disease
brain insulin resistance
<i>db/db</i> diabetic mouse model
diabetic cognopathy
insulin resistance
metabolic syndrome
mixed dementia
obesity
type 2 diabetes mellitus
url https://www.mdpi.com/2076-3425/9/10/262
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