Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects elderly persons, evolving with age to reach severe cognitive impairment. Amyloid deposits and neurofibrillary tangles constitute the main pathological hallmarks of AD. Amyloid deposits are initiated by the excessive production and accumulation of beta-amyloid (Aβ) peptides in the brain. The dysfunction of the Neurovascular Unit (NVU) has been proposed to be causative in AD development, due to an impaired clearance of Aβ from the brain. Cells forming the NVU express several Adenosine Triphosphate ATP-Binding Cassette (ABC) transporters, among which ABCB1 and ABCA1 play an important role in Aβ processing. The drug transporter ABCB1 directly transports Aβ from the brain into the blood circulation, whereas the cholesterol transporter ABCA1 neutralizes Aβ aggregation capacity in an Apolipoprotein E (ApoE)-dependent manner, facilitating Aβ subsequent elimination from the brain. In the present minireview, we will summarize the contribution of ABCB1, and ABCA1 at the NVU in Aβ clearance. Moreover, we will outline and discuss the possible collaboration of ABCB1, and ABCA1 at the NVU in mediating an efficient clearance of Aβ from the brain.
Highlights
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that affects elderly persons
A clinical study conducted in AD patients with mild cognitive deficits concluded that both doxycycline and rifampicin efficaciously reduce the cognitive decline in treated patients (Loeb et al, 2004), possibly and partly via a mechanism involving ABC transporter subfamily B member 1 (ABCB1), as both molecules have been reported to induce ABCB1 expression (Wolf et al, 2012)
The expression of ABCB1 and ABC transporter sub-family A member 1 (ABCA1) in all cells forming the Neurovascular Unit (NVU) is of high importance, because it would constitute an elegant mechanism via which the ABCA1/Apolipoprotein E (ApoE) and lipoprotein-related protein-1 (LRP-1)/ABCB1 systems work in concert and cooperate to facilitate Aβ transport from plaques towards brain microvessels, and its subsequent clearance into blood circulation
Summary
Laboratory of Neurosciences, Department of Molecular Medicine, Faculty of Medicine, CHU de Québec Research Center, Laval University, Québec, QC, Canada. Amyloid deposits are initiated by the excessive production and accumulation of beta-amyloid (Aβ) peptides in the brain. The dysfunction of the Neurovascular Unit (NVU) has been proposed to be causative in AD development, due to an impaired clearance of Aβ from the brain. Cells forming the NVU express several Adenosine Triphosphate ATP-Binding Cassette (ABC) transporters, among which ABCB1 and ABCA1 play an important role in Aβ processing. We will summarize the contribution of ABCB1, and ABCA1 at the NVU in Aβ clearance. We will outline and discuss the possible collaboration of ABCB1, and ABCA1 at the NVU in mediating an efficient clearance of Aβ from the brain
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