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Neurobiol Dis. 2014 Dec;72 Pt A:54-60. doi: 10.1016/j.nbd.2014.04.001. Epub 2014 Apr 16.

Alzheimer's and ABC transporters--new opportunities for diagnostics and treatment.

Author information

1
Neurodegeneration Research Lab (NRL), Department of Neurology, University of Magdeburg, Leipziger Str. 44, Bldg. 64, 39120 Magdeburg, Germany; German Center for Neurodegenerative Diseases (DZNE) Magdeburg, Leipziger Str. 44, Bldg. 64, 39120 Magdeburg, Germany. Electronic address: jens.pahnke@web.de.
2
Health and Environment Department, AIT - Austrian Institute of Technology GmbH, 2444 Seibersdorf, Austria; Department of Clinical Pharmacology, Medical University of Vienna, Währinger-Gürtel 18-20, 1090 Vienna, Austria.
3
Neurodegeneration Research Lab (NRL), Department of Neurology, University of Magdeburg, Leipziger Str. 44, Bldg. 64, 39120 Magdeburg, Germany.

Abstract

Much has been said about the increasing number of demented patients and the main risk factor 'age'. Frustratingly, we do not know the precise pattern and all modulating factors that provoke the pathologic changes in the brains of affected elderly. We have to diagnose early to be able to stop the progression of diseases that irreversibly destroy brain substance. Familiar AD cases have mislead some researchers for almost 20 years, which has unfortunately narrowed the scientific understanding and has, thus, lead to insufficient funding of independent approaches. Therefore, basic researchers hardly have been able to develop causative treatments and clinicians still do not have access to prognostic and early diagnostic tools. During the recent years it became clear that insufficient Aβ export, physiologically facilitated by the ABC transporter superfamily at the brain's barriers, plays a fundamental role in disease initiation and progression. Furthermore, export mechanisms that are deficient in affected elderly are new targets for activation and, thus, treatment, but ideally also for prevention. In sporadic AD disturbed clearance of β-amyloid from the brain is so far the most important factor for its accumulation in the parenchyma and vessel walls. Here, we review findings about the contribution of ABC transporters and of the perivascular drainage/glymphatic system on β-amyloid clearance. We highlight their potential value for innovative early diagnostics using PET and describe recently described, effective ABC transporter-targeting agents as potential causative treatment for neurodegenerative proteopathies/dementias.

KEYWORDS:

ABC transporter; ABCA7; ABCB1; ABCC1; Alzheimer’s disease; Amyloid-beta; BBB; Blood–brain barrier; Choroid plexus; Glymphatic system; Neurodegeneration; PET

PMID:
24746857
PMCID:
PMC4199932
DOI:
10.1016/j.nbd.2014.04.001
[Indexed for MEDLINE]
Free PMC Article

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