title: Targeting ApoE4/ApoE receptor LRP1 in Alzheimer's disease.
abstract: BACKGROUND
  Progressive neuronal loss is a key feature in Alzheimer's disease (AD), which is the most common neurodegenerative disorder in the aging population. Currently, there are no therapeutic means to intervene neuronal damage in AD and therefore innovative approaches to discover novel strategies for the treatment of AD are needed. Based on the prevailing amyloid cascade hypothesis, it is conceivable that lowering the β-amyloid (Aβ) levels is sufficient to slow down the disease process, if started early enough.
  
  
  METHODS
  Here, we review genetic and biological functions related to apolipoprotein E (ApoE) and low-density lipoprotein receptor-related protein 1 receptor (LRP1)-mediated clearance of Aβ. Furthermore, we discuss the AD-related therapeutic potential of targeting to ApoE receptor LRP1 at the blood-brain barrier (BBB) and in the periphery.
  
  
  CONCLUSIONS
  Due to the recent setbacks in the clinical trials targeting AD, it is instrumental to seek alternative therapeutic approaches, which aim to reduce the accumulation of Aβ in the brain tissue. As the ApoE/LRP1-mediated clearance of Aβ across the BBB is the key event in the regulation of Aβ transcytosis from brain to periphery, direct targeting of this protein entity at the BBB holds a great potential in the treatment of AD.
authors.affiliation: Kuopio University Hospital, Institute of Clinical Medicine-Neurology, University of Eastern Finland and Department of Neurology, Kuopio, Finland.
authors.forename: Henna
authors.initials: H
authors.lastname: Martiskainen
authors.forename: Annakaisa
authors.initials: A
authors.lastname: Haapasalo
authors.forename: Kaisa M A
authors.initials: KM
authors.lastname: Kurkinen
authors.forename: Jussi
authors.initials: J
authors.lastname: Pihlajamäki
authors.forename: Hilkka
authors.initials: H
authors.lastname: Soininen
authors.forename: Mikko
authors.initials: M
authors.lastname: Hiltunen
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D053327:Apolipoprotein E4 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; C475476:LRP1 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1