PMID- 31569571
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2076-3425 (Print)
IS  - 2076-3425 (Electronic)
IS  - 2076-3425 (Linking)
VI  - 9
IP  - 10
DP  - 2019 Sep 29
TI  - Type 2 Diabetes Mellitus Increases The Risk of Late-Onset Alzheimer's Disease: 
      Ultrastructural Remodeling of the Neurovascular Unit and Diabetic Gliopathy.
LID - 10.3390/brainsci9100262 [doi]
LID - 262
AB  - 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 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 db/db 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'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-nitrogen species); iv. inflammation (peripheral 
      macrophage and central brain microglia); v. vascular (macrovascular accelerated 
      atherosclerosis-vascular stiffening and microvascular NVU/neuroglial remodeling) 
      with resulting impaired cerebral blood flow.
FAU - Hayden, Melvin R
AU  - Hayden MR
AD  - Diabetes and Cardiovascular Center, University of Missouri School of Medicine, 
      Columbia, MO 65212, USA. mrh29pete@gmail.com.
AD  - Division of Endocrinology and Metabolism, Department of Medicine, University of 
      Missouri, Columbia, MO 65212, USA. mrh29pete@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20190929
PL  - Switzerland
TA  - Brain Sci
JT  - Brain sciences
JID - 101598646
PMC - PMC6826500
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - aging
OT  - brain insulin resistance
OT  - db/db diabetic mouse model
OT  - diabetic cognopathy
OT  - insulin resistance
OT  - metabolic syndrome
OT  - mixed dementia
OT  - obesity
OT  - type 2 diabetes mellitus
COIS- The author declares no conflict of interest.
EDAT- 2019/10/02 06:00
MHDA- 2019/10/02 06:01
PMCR- 2019/10/01
CRDT- 2019/10/02 06:00
PHST- 2019/09/06 00:00 [received]
PHST- 2019/09/17 00:00 [revised]
PHST- 2019/09/27 00:00 [accepted]
PHST- 2019/10/02 06:00 [entrez]
PHST- 2019/10/02 06:00 [pubmed]
PHST- 2019/10/02 06:01 [medline]
PHST- 2019/10/01 00:00 [pmc-release]
AID - brainsci9100262 [pii]
AID - brainsci-09-00262 [pii]
AID - 10.3390/brainsci9100262 [doi]
PST - epublish
SO  - Brain Sci. 2019 Sep 29;9(10):262. doi: 10.3390/brainsci9100262.