ApoE and cerebral insulin: Trafficking, receptors, and resistance

NEUROBIOLOGY OF DISEASE

卷:137

Review

Rhea, Elizabeth M.^1,2  Raber, Jacob^3,4,5  Banks, William A.^1,2 

[1] Vet Affairs Puget Sound Healthcare Syst, Res & Dev, Seattle, WA 98108 USA

[2] Univ Washington, Dept Med, Seattle, WA 98195 USA

[3] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA

[4] Oregon Hlth & Sci Univ, Div Neurosci, Dept Neurol, ONPRC, Portland, OR 97239 USA

[5] Oregon Hlth & Sci Univ, Div Neurosci, Dept Radiat Med, ONPRC, Portland, OR 97239 USA

关键词: Apolipoprotein E;    Central nervous system insulin;    Insulin receptor;    Blood-brain barrier;    Alzheimer's disease;    Amyloid beta;   

DOI  :  10.1016/j.nbd.2020.104755

来源: Elsevier

【 摘 要 】

Central nervous system (CNS) insulin resistance is associated with Alzheimer's disease (AD). In addition, the apolipoprotein E4 (apoE4) isoform is a risk factor for AD. The connection between these two factors in relation to AD is being actively explored. We summarize this literature with a focus on the transport of insulin and apoE across the blood-brain barrier (BBB) and into the CNS, the impact of apoE and insulin on the BBB, and the interactions between apoE, insulin, and the insulin receptor once present in the CNS. We highlight how CNS insulin resistance is apparent in AD and potential ways to overcome this resistance by repurposing currently approved drugs, with apoE genotype taken into consideration as the treatment response following most interventions is apoE isoform-dependent. This review is part of a special issue focusing on apoE in AD and neuro-degeneration.