Pathophysiology (Oct 2024)

Pathways to Alzheimer’s Disease: The Intersecting Roles of Clusterin and Apolipoprotein E in Amyloid-β Regulation and Neuronal Health

  • Alexandru Laslo,
  • Laura Laslo,
  • Eliza-Mihaela Arbănași,
  • Alexandru-Andrei Ujlaki-Nagi,
  • Laura Chinezu,
  • Adrian Dumitru Ivănescu,
  • Emil-Marian Arbănași,
  • Roxana Octavia Cărare,
  • Bogdan Andrei Cordoș,
  • Ioana Adriana Popa,
  • Klara Brînzaniuc

DOI
https://doi.org/10.3390/pathophysiology31040040
Journal volume & issue
Vol. 31, no. 4
pp. 545 – 558

Abstract

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One of the hallmarks of Alzheimer’s disease (AD) is the deposition of amyloid-β (Aβ) within the extracellular spaces of the brain as plaques and along the blood vessels in the brain, a condition also known as cerebral amyloid angiopathy (CAA). Clusterin (CLU), or apolipoprotein J (APOJ), is a multifunctional glycoprotein that has a role in many physiological and neurological conditions, including AD. The apolipoprotein E (APOE) is a significant genetic factor in AD, and while the primary physiological role of APOE in the brain and peripheral tissues is to regulate lipid transport, it also participates in various other biological processes, having three basic human forms: APOE2, APOE3, and APOE4. Notably, the APOE4 allele substantially increases the risk of developing late-onset AD. The main purpose of this review is to examine the roles of CLU and APOE in AD pathogenesis in order to acquire a better understanding of AD pathogenesis from which to develop targeted therapeutic approaches.

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