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Comment
. 2023 Aug;39(8):1330-1332.
doi: 10.1007/s12264-023-01058-1. Epub 2023 Apr 24.

Peripheral ApoE4 Leads to Cerebrovascular Dysfunction and Aβ Deposition in Alzheimer's Disease

Rui Sun  1 , Chunming Xie  2   3   4
Affiliations
Comment

Peripheral ApoE4 Leads to Cerebrovascular Dysfunction and Aβ Deposition in Alzheimer's Disease

Rui Sun et al. Neurosci Bull. 2023 Aug.
No abstract available

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Conflict of interest statement

All authors declare no competing interest.

Figures

Fig. 1
Fig. 1
Peripheral apoE4 drives Alzheimer’s pathology by impairing cerebrovascular function. ApoE4 is the most important genetic risk factor for late-onset AD. Liu et al. constructed liver-specific expression of human apoE3 or apoE4 in mice in the context of apoE knockout, ensuring that apoE3 or apoE4 was expressed only in the liver and secreted into the blood. To further explore the underlying pathological mechanism by which liver-expressed apoE4 disrupts brain function, Liu et al. studied cerebral vascular permeability. Increased leakage of the BBB and levels of albumin in perivascular areas were found in iE4 mice. Then, decreased levels of the tight junction proteins claudin-5 (CLDN5) and zonula occludens1 (ZO1) in endothelial cells were also found in iE4 mice. Meanwhile, increased deposition of perivascular IgG also occurred in iE4 mice. Moreover, iE4 mice were also found to have a lower frequency of vasodilation of cerebral arterioles and significantly reduced numbers of vascular branches, which may lead to decreased arterial cerebral blood flow. In addition, the peripheral apoE4 may promote vascular inflammation, thereby transducing inflammatory signals to the brain and the activation of astrocytes and microglia. These together lead to increased Aβ deposition. In conclusion, liver-expressed apoE4 disrupts synaptic plasticity and cognitive function by impairing cerebrovascular function and exacerbating brain amyloid pathology.
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Comment on

  • Peripheral apoE4 enhances Alzheimer's pathology and impairs cognition by compromising cerebrovascular function.
    Liu CC, Zhao J, Fu Y, Inoue Y, Ren Y, Chen Y, Doss SV, Shue F, Jeevaratnam S, Bastea L, Wang N, Martens YA, Qiao W, Wang M, Zhao N, Jia L, Yamazaki Y, Yamazaki A, Rosenberg CL, Wang Z, Kong D, Li Z, Kuchenbecker LA, Trottier ZA, Felton L, Rogers J, Quicksall ZS, Linares C, Knight J, Chen Y, Kurti A, Kanekiyo T, Fryer JD, Asmann YW, Storz P, Wang X, Peng J, Zhang B, Kim BYS, Bu G. Liu CC, et al. Nat Neurosci. 2022 Aug;25(8):1020-1033. doi: 10.1038/s41593-022-01127-0. Epub 2022 Aug 1. Nat Neurosci. 2022. PMID: 35915180 Free PMC article.

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