The Blood-Brain Barrier in Alzheimer's Disease

Handb Exp Pharmacol. 2022:273:247-266. doi: 10.1007/164_2020_418.

Abstract

The accumulation of neurotoxic amyloid-beta (Aβ) in the brain is one of the characteristic hallmarks of Alzheimer's disease (AD). Aβ-peptide brain homeostasis is governed by its production and various clearance mechanisms. The blood-brain barrier provides a large surface area for influx and efflux mechanisms into and out of the brain. Different transporters and receptors have been implicated to play crucial roles in Aβ clearance from brain. Besides Aβ transport, the blood-brain barrier tightly regulates the brain's microenvironment; however, vascular alterations have been shown in patients with AD. Here, we summarize how the blood-brain barrier changes during aging and in disease and focus on recent findings of how the ABC transporter P-glycoprotein (ABCB1/P-gp) and the receptor low-density lipoprotein receptor-related protein 1 (LRP1) play a role in Aβ clearance from brain.

Keywords: Alzheimer’s disease (AD); Amyloid-beta (Aβ); Blood-brain barrier; Clearance; LRP1; Neurovascular unit; P-gp/ABCB1.

MeSH terms

  • Alzheimer Disease*
  • Amyloid beta-Peptides
  • Blood-Brain Barrier / metabolism
  • Brain / metabolism
  • Humans
  • Peptide Fragments / metabolism
  • Receptors, LDL / metabolism

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • Receptors, LDL