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Apolipoprotein E4 disrupts the neuroprotective action of sortilin in neuronal lipid metabolism and endocannabinoid signaling

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Apolipoprotein E4 disrupts the neuroprotective action of sortilin in neuronal lipid metabolism and endocannabinoid signaling. / Asaro, Antonino; Carlo-Spiewok, Anne-Sophie; Malik, Anna R; Rothe, Michael; Schipke, Carola G; Peters, Oliver; Heeren, Joerg; Willnow, Thomas E.

In: ALZHEIMERS DEMENT, Vol. 16, No. 9, 09.2020, p. 1248-1258.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Asaro, A, Carlo-Spiewok, A-S, Malik, AR, Rothe, M, Schipke, CG, Peters, O, Heeren, J & Willnow, TE 2020, 'Apolipoprotein E4 disrupts the neuroprotective action of sortilin in neuronal lipid metabolism and endocannabinoid signaling', ALZHEIMERS DEMENT, vol. 16, no. 9, pp. 1248-1258. https://doi.org/10.1002/alz.12121

APA

Asaro, A., Carlo-Spiewok, A-S., Malik, A. R., Rothe, M., Schipke, C. G., Peters, O., Heeren, J., & Willnow, T. E. (2020). Apolipoprotein E4 disrupts the neuroprotective action of sortilin in neuronal lipid metabolism and endocannabinoid signaling. ALZHEIMERS DEMENT, 16(9), 1248-1258. https://doi.org/10.1002/alz.12121

Vancouver

Asaro A, Carlo-Spiewok A-S, Malik AR, Rothe M, Schipke CG, Peters O et al. Apolipoprotein E4 disrupts the neuroprotective action of sortilin in neuronal lipid metabolism and endocannabinoid signaling. ALZHEIMERS DEMENT. 2020 Sep;16(9):1248-1258. https://doi.org/10.1002/alz.12121

Bibtex

@article{21d8fcca96db43cf9e37d822d5c73286,
title = "Apolipoprotein E4 disrupts the neuroprotective action of sortilin in neuronal lipid metabolism and endocannabinoid signaling",
abstract = "INTRODUCTION: Apolipoprotein E (apoE) is a carrier for brain lipids and the most important genetic risk factor for Alzheimer's disease (AD). ApoE binds the receptor sortilin, which mediates uptake of apoE-bound cargo into neurons. The significance of this uptake route for brain lipid homeostasis and AD risk seen with apoE4, but not apoE3, remains unresolved.METHODS: Combining neurolipidomics in patient specimens with functional studies in mouse models, we interrogated apoE isoform-specific functions for sortilin in brain lipid metabolism and AD.RESULTS: Sortilin directs the uptake and conversion of polyunsaturated fatty acids into endocannabinoids, lipid-based neurotransmitters that act through nuclear receptors to sustain neuroprotective gene expression in the brain. This sortilin function requires apoE3, but is disrupted by binding of apoE4, compromising neuronal endocannabinoid metabolism and action.DISCUSSION: We uncovered the significance of neuronal apoE receptor sortilin in facilitating neuroprotective actions of brain lipids, and its relevance for AD risk seen with apoE4.",
author = "Antonino Asaro and Anne-Sophie Carlo-Spiewok and Malik, {Anna R} and Michael Rothe and Schipke, {Carola G} and Oliver Peters and Joerg Heeren and Willnow, {Thomas E}",
note = "{\textcopyright} 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",
year = "2020",
month = sep,
doi = "10.1002/alz.12121",
language = "English",
volume = "16",
pages = "1248--1258",
journal = "ALZHEIMERS DEMENT",
issn = "1552-5260",
publisher = "Elsevier Inc.",
number = "9",

}

RIS

TY - JOUR

T1 - Apolipoprotein E4 disrupts the neuroprotective action of sortilin in neuronal lipid metabolism and endocannabinoid signaling

AU - Asaro, Antonino

AU - Carlo-Spiewok, Anne-Sophie

AU - Malik, Anna R

AU - Rothe, Michael

AU - Schipke, Carola G

AU - Peters, Oliver

AU - Heeren, Joerg

AU - Willnow, Thomas E

N1 - © 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

PY - 2020/9

Y1 - 2020/9

N2 - INTRODUCTION: Apolipoprotein E (apoE) is a carrier for brain lipids and the most important genetic risk factor for Alzheimer's disease (AD). ApoE binds the receptor sortilin, which mediates uptake of apoE-bound cargo into neurons. The significance of this uptake route for brain lipid homeostasis and AD risk seen with apoE4, but not apoE3, remains unresolved.METHODS: Combining neurolipidomics in patient specimens with functional studies in mouse models, we interrogated apoE isoform-specific functions for sortilin in brain lipid metabolism and AD.RESULTS: Sortilin directs the uptake and conversion of polyunsaturated fatty acids into endocannabinoids, lipid-based neurotransmitters that act through nuclear receptors to sustain neuroprotective gene expression in the brain. This sortilin function requires apoE3, but is disrupted by binding of apoE4, compromising neuronal endocannabinoid metabolism and action.DISCUSSION: We uncovered the significance of neuronal apoE receptor sortilin in facilitating neuroprotective actions of brain lipids, and its relevance for AD risk seen with apoE4.

AB - INTRODUCTION: Apolipoprotein E (apoE) is a carrier for brain lipids and the most important genetic risk factor for Alzheimer's disease (AD). ApoE binds the receptor sortilin, which mediates uptake of apoE-bound cargo into neurons. The significance of this uptake route for brain lipid homeostasis and AD risk seen with apoE4, but not apoE3, remains unresolved.METHODS: Combining neurolipidomics in patient specimens with functional studies in mouse models, we interrogated apoE isoform-specific functions for sortilin in brain lipid metabolism and AD.RESULTS: Sortilin directs the uptake and conversion of polyunsaturated fatty acids into endocannabinoids, lipid-based neurotransmitters that act through nuclear receptors to sustain neuroprotective gene expression in the brain. This sortilin function requires apoE3, but is disrupted by binding of apoE4, compromising neuronal endocannabinoid metabolism and action.DISCUSSION: We uncovered the significance of neuronal apoE receptor sortilin in facilitating neuroprotective actions of brain lipids, and its relevance for AD risk seen with apoE4.

U2 - 10.1002/alz.12121

DO - 10.1002/alz.12121

M3 - SCORING: Journal article

C2 - 32588544

VL - 16

SP - 1248

EP - 1258

JO - ALZHEIMERS DEMENT

JF - ALZHEIMERS DEMENT

SN - 1552-5260

IS - 9

ER -