ABCA7 and pathogenic pathways of Alzheimer’s disease

Tomonori Aikawa, Marie Louise Holm, Takahisa Kanekiyo

Research output: Contribution to journalReview article

13 Citations (Scopus)

Abstract

The ATP‐binding cassette (ABC) reporter family functions to regulate the homeostasis of phospholipids and cholesterol in the central nervous system, as well as peripheral tissues. ABCA7 belongs to the A subfamily of ABC transporters, which shares 54% sequence identity with ABCA1. While ABCA7 is expressed in a variety of tissues/organs, including the brain, recent genome‐wide association studies (GWAS) have identified ABCA7 gene variants as susceptibility loci for late‐onset Alzheimer’s disease (AD). More important, subsequent genome sequencing analyses have revealed that premature termination codon mutations in ABCA7 are associated with the increased risk for AD. Alzheimer’s disease is a progressive neurodegenerative disease and the most common cause of dementia, where the accumulation and deposition of amyloid‐β (Aβ) peptides cleaved from amyloid precursor protein (APP) in the brain trigger the pathogenic cascade of the disease. In consistence with human genetic studies, increasing evidence has demonstrated that ABCA7 deficiency exacerbates Aβ pathology using in vitro and in vivo models. While ABCA7 has been shown to mediate phagocytic activity in macrophages, ABCA7 is also involved in the microglial Aβ clearance pathway. Furthermore, ABCA7 deficiency results in accelerated Aβ production, likely by facilitating endocytosis and/or processing of APP. Taken together, current evidence suggests that ABCA7 loss‐of‐function contributes to AD‐related phenotypes through multiple pathways. A better understanding of the function of ABCA7 beyond lipid metabolism in both physiological and pathological conditions becomes increasingly important to explore AD pathogenesis.

Original languageEnglish (US)
Article number27
JournalBrain Sciences
Volume8
Issue number2
DOIs
StatePublished - Feb 1 2018

Fingerprint

Alzheimer Disease
Amyloid beta-Protein Precursor
Nonsense Codon
Medical Genetics
Brain
Endocytosis
Lipid Metabolism
Amyloid
Neurodegenerative Diseases
Dementia
Phospholipids
Homeostasis
Central Nervous System
Macrophages
Cholesterol
Genome
Pathology
Phenotype
Peptides
Mutation

Keywords

  • ABCA1
  • Amyloid precursor protein
  • Amyloid‐β
  • Cholesterol
  • Genetics
  • Macrophage
  • Microglia
  • Neurons
  • Phagocytosis
  • Phospholipids

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

ABCA7 and pathogenic pathways of Alzheimer’s disease. / Aikawa, Tomonori; Holm, Marie Louise; Kanekiyo, Takahisa.

In: Brain Sciences, Vol. 8, No. 2, 27, 01.02.2018.

Research output: Contribution to journalReview article

Aikawa, Tomonori ; Holm, Marie Louise ; Kanekiyo, Takahisa. / ABCA7 and pathogenic pathways of Alzheimer’s disease. In: Brain Sciences. 2018 ; Vol. 8, No. 2.
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