PMID- 37611907
OWN - NLM
STAT- Publisher
LR  - 20240425
IS  - 2152-5250 (Print)
IS  - 2152-5250 (Linking)
DP  - 2023 Aug 17
TI  - State of the Science on Brain Insulin Resistance and Cognitive Decline Due to 
      Alzheimer's Disease.
LID - 10.14336/AD.2023.0814 [doi]
AB  - Type 2 diabetes mellitus (T2DM) is common and increasing in prevalence worldwide, 
      with devastating public health consequences. While peripheral insulin resistance 
      is a key feature of most forms of T2DM and has been investigated for over a 
      century, research on brain insulin resistance (BIR) has more recently been 
      developed, including in the context of T2DM and non-diabetes states. Recent data 
      support the presence of BIR in the aging brain, even in non-diabetes states, and 
      found that BIR may be a feature in Alzheimer's disease (AD) and contributes to 
      cognitive impairment. Further, therapies used to treat T2DM are now being 
      investigated in the context of AD treatment and prevention, including insulin. In 
      this review, we offer a definition of BIR, and present evidence for BIR in AD; we 
      discuss the expression, function, and activation of the insulin receptor (INSR) 
      in the brain; how BIR could develop; tools to study BIR; how BIR correlates with 
      current AD hallmarks; and regional/cellular involvement of BIR. We close with a 
      discussion on resilience to both BIR and AD, how current tools can be improved to 
      better understand BIR, and future avenues for research. Overall, this review and 
      position paper highlights BIR as a plausible therapeutic target for the 
      prevention of cognitive decline and dementia due to AD.
FAU - Rhea, Elizabeth M
AU  - Rhea EM
AD  - Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound 
      Health Care System, Seattle, WA 98108, USA.
AD  - Department of Medicine, Division of Gerontology and Geriatric Medicine, 
      University of Washington, Seattle, WA 98195, USA.
FAU - Leclerc, Manon
AU  - Leclerc M
AD  - Faculty of Pharmacy, Laval University, Quebec, Quebec, Canada.
AD  - Neuroscience Axis, CHU de Quebec Research Center - Laval University, Quebec, 
      Quebec, Canada.
FAU - Yassine, Hussein N
AU  - Yassine HN
AD  - Departments of Neurology and Medicine, University of Southern California, Los 
      Angeles, CA 90033, USA.
FAU - Capuano, Ana W
AU  - Capuano AW
AD  - Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL 
      60612, USA.
FAU - Tong, Han
AU  - Tong H
AD  - Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL 
      60612, USA.
FAU - Petyuk, Vladislav A
AU  - Petyuk VA
AD  - Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 
      99352, USA.
FAU - Macauley, Shannon L
AU  - Macauley SL
AD  - Department of Physiology, University of Kentucky, Lexington, KY 40508, USA.
FAU - Fioramonti, Xavier
AU  - Fioramonti X
AD  - Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000 Bordeaux, 
      France.
AD  - International Associated Laboratory OptiNutriBrain, Bordeaux, France and Quebec, 
      Canada.
FAU - Carmichael, Owen
AU  - Carmichael O
AD  - Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
FAU - Calon, Frederic
AU  - Calon F
AD  - Faculty of Pharmacy, Laval University, Quebec, Quebec, Canada.
AD  - Neuroscience Axis, CHU de Quebec Research Center - Laval University, Quebec, 
      Quebec, Canada.
AD  - International Associated Laboratory OptiNutriBrain, Bordeaux, France and Quebec, 
      Canada.
FAU - Arvanitakis, Zoe
AU  - Arvanitakis Z
AD  - Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL 
      60612, USA.
LA  - eng
GR  - P30 AG072946/AG/NIA NIH HHS/United States
GR  - RF1 AG074549/AG/NIA NIH HHS/United States
GR  - RF1 AG059621/AG/NIA NIH HHS/United States
GR  - R01 AG068330/AG/NIA NIH HHS/United States
GR  - P30 DK017047/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20230817
PL  - United States
TA  - Aging Dis
JT  - Aging and disease
JID - 101540533
EDAT- 2023/08/24 00:42
MHDA- 2023/08/24 00:42
CRDT- 2023/08/23 19:33
PHST- 2023/06/02 00:00 [received]
PHST- 2023/08/14 00:00 [accepted]
PHST- 2023/08/24 00:42 [medline]
PHST- 2023/08/24 00:42 [pubmed]
PHST- 2023/08/23 19:33 [entrez]
AID - AD.2023.0814 [pii]
AID - 10.14336/AD.2023.0814 [doi]
PST - aheadofprint
SO  - Aging Dis. 2023 Aug 17. doi: 10.14336/AD.2023.0814.