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Review
. 2020 Sep;19(9):758-766.
doi: 10.1016/S1474-4422(20)30231-3. Epub 2020 Jul 27.

Brain insulin resistance in Alzheimer's disease and related disorders: mechanisms and therapeutic approaches

Derek Kellar  1 , Suzanne Craft  2
Affiliations
Review

Brain insulin resistance in Alzheimer's disease and related disorders: mechanisms and therapeutic approaches

Derek Kellar et al. Lancet Neurol. 2020 Sep.

Abstract

Insulin is a peptide secreted by the pancreas and plays an important role in the regulation of glucose metabolism in peripheral tissues. Although the role of insulin in the periphery is well understood, less is known about its multifactorial role in the brain. However, emerging evidence from human and animal studies indicate that insulin influences cerebral bioenergetics, enhances synaptic viability and dendritic spine formation, and increases turnover of neurotransmitters, such as dopamine. Insulin also has a role in proteostasis, influencing clearance of the amyloid β peptide and phosphorylation of tau, which are hallmarks of Alzheimer's disease. Insulin also modulates vascular function through effects on vasoreactivity, lipid metabolism, and inflammation. Through these multiple pathways, insulin dysregulation could contribute to neurodegeneration. Thus, new approaches to restore cerebral insulin function that could offer therapeutic benefit to adults with Alzheimer's disease, vascular cognitive impairment, or related disorders are being investigated.

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Conflict of interest statement

Declaration of interests

We declare no competing interests.

Figures

Figure:
Figure:. Association between insulin resistance and Alzheimer’s disease and related disorders
BBB=blood-brain barrier.
See this image and copyright information in PMC

Comment in

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