Accessible Requires Authentication Published by De Gruyter January 8, 2020

Apolipoprotein E: Cholesterol metabolism and Alzheimer’s pathology

Theresa Pohlkamp
From the journal Neuroforum

Abstract

Age is the greatest risk factor for Alzheimer’s disease (AD). Today, due to an increase in global life expectancy, AD-related deaths are ranked as the sixth most common cause of death. The allele isoform ɛ4 of apolipoprotein E (ApoE4) is the most important genetic risk factor for AD. Three ApoE isoforms are common in humans: ApoE2, ApoE3, and ApoE4. ApoE3 is the most frequent isoform and considered neutral with regards to AD, whereas the isoform ApoE2 is protective. Thus it is important to understand how ApoE isoforms affect amyloid-β (Aβ) and tau toxicity, the key drivers of AD pathology. Aβ and tau accumulate to form the hallmarks of AD, plaques and neurofibrillary tangles, respectively. ApoE, primarily expressed by astrocytes, is the major lipid transporter in the brain. In this review I summarize some important historic and scientific aspects of our progress in understanding the role of the cholesterol transporter ApoE in the brain, and how the isoform ApoE4 contributes to AD pathology.

Zusammenfassung

Je älter man wird, desto größer ist die Chance an Alzheimer Demenz (AD) zu erkranken. Aufgrund steigender Lebenserwartung ist AD heute eine der häufigsten Todesursachen weltweit. Die Apolipoprotein E (ApoE) Allelvariante ɛ4 ist der stärkste genetische AD-Risikofaktor. Der Fetttransporter ApoE existiert in drei Allelvarianten: ApoE2, ApoE3 und ApoE4. Die häufigste Form ApoE3 wird im Zusammenhang mit AD als neutral betrachtet, während ApoE2 schützend wirkt. Daher ist es wichtig zu verstehen, wie die verschiedenen ApoE-Varianten zu der Toxizität von Amyloid-β (Aβ) und Tau beitragen. Aβ und Tau akkumulieren in Plaques bzw. bilden intraneuronale Fibrillen, die zusammen die pathologischen Hauptmerkmale von AD darstellen. Überwiegend von Astrozyten produziert, ist ApoE der wichtigste Lipidtransporter im Gehirn. In diesem Review-Artikel erläutere ich den wissenschaftlichen Fortschritt zum Verständnis der Funktion des Cholesterintransporters ApoE im Gehirn und welche Rolle ApoE4 in der AD-Pathologie spielt.

Acknowledgements

I thank Judith Bohnacker and Kristina Kuhbandner for their feedback.

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Published Online: 2020-01-08
Published in Print: 2020-02-25

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