ApoE4 Accelerates Early Seeding of Amyloid Pathology

Chia-Chen Liu, Na Zhao, Yuan Fu, Na Wang, Cynthia Linares, Chih Wei Tsai, Guojun D Bu

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Accumulation and aggregation of amyloid-β (Aβ) in the brain is an initiating step in the pathogenesis of Alzheimer's disease (AD). The ε4 allele of apolipoprotein E (apoE) gene is the strongest genetic risk factor for late-onset AD. Although there is strong evidence showing that apoE4 enhances amyloid pathology, it is not clear what the critical stage(s) is during amyloid development in which apoE4 has the strongest impact. Using apoE inducible mouse models, we show that increased expression of astrocytic apoE4, but not apoE3, during the seeding stage of amyloid development enhanced amyloid deposition and neuritic dystrophy in amyloid model mice. ApoE4, but not apoE3, significantly increased brain Aβ half-life measured by in vivo microdialysis. Furthermore, apoE4 expression increased whereas apoE3 reduced amyloid-related gliosis in the mouse brains. Together, our results demonstrate that apoE4 has the greatest impact on amyloid during the seeding stage, likely by perturbing Aβ clearance and enhancing Aβ aggregation. Liu et al. have developed cell-type-specific and inducible apoE mouse models and demonstrate that astrocytic apoE4 is a potent factor in promoting amyloidosis during the seeding stage, but not the rapid growth period, of amyloid development. ApoE4 impairs Aβ clearance and accelerates Aβ aggregation, leading to enhanced amyloid pathology and neuritic dystrophy.

Original languageEnglish (US)
Pages (from-to)1024-1032.e3
JournalNeuron
Volume96
Issue number5
DOIs
StatePublished - Dec 6 2017

Fingerprint

Apolipoprotein E4
Amyloid
Pathology
Apolipoprotein E3
Apolipoproteins E
Alzheimer Disease
Brain
Gliosis
Microdialysis
Amyloidosis
Half-Life
Alleles

Keywords

  • Alzheimer's disease
  • amyloid pathology
  • apolipoprotein E
  • seeding

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Liu, C-C., Zhao, N., Fu, Y., Wang, N., Linares, C., Tsai, C. W., & Bu, G. D. (2017). ApoE4 Accelerates Early Seeding of Amyloid Pathology. Neuron, 96(5), 1024-1032.e3. https://doi.org/10.1016/j.neuron.2017.11.013

ApoE4 Accelerates Early Seeding of Amyloid Pathology. / Liu, Chia-Chen; Zhao, Na; Fu, Yuan; Wang, Na; Linares, Cynthia; Tsai, Chih Wei; Bu, Guojun D.

In: Neuron, Vol. 96, No. 5, 06.12.2017, p. 1024-1032.e3.

Research output: Contribution to journalArticle

Liu, C-C, Zhao, N, Fu, Y, Wang, N, Linares, C, Tsai, CW & Bu, GD 2017, 'ApoE4 Accelerates Early Seeding of Amyloid Pathology', Neuron, vol. 96, no. 5, pp. 1024-1032.e3. https://doi.org/10.1016/j.neuron.2017.11.013
Liu C-C, Zhao N, Fu Y, Wang N, Linares C, Tsai CW et al. ApoE4 Accelerates Early Seeding of Amyloid Pathology. Neuron. 2017 Dec 6;96(5):1024-1032.e3. https://doi.org/10.1016/j.neuron.2017.11.013
Liu, Chia-Chen ; Zhao, Na ; Fu, Yuan ; Wang, Na ; Linares, Cynthia ; Tsai, Chih Wei ; Bu, Guojun D. / ApoE4 Accelerates Early Seeding of Amyloid Pathology. In: Neuron. 2017 ; Vol. 96, No. 5. pp. 1024-1032.e3.
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