title: Alzheimer's and ABC transporters--new opportunities for diagnostics and treatment.
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.
authors.affiliation: 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.
authors.forename: Jens
authors.initials: J
authors.lastname: Pahnke
authors.affiliation: 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.
authors.forename: Oliver
authors.initials: O
authors.lastname: Langer
authors.affiliation: Neurodegeneration Research Lab (NRL), Department of Neurology, University of Magdeburg, Leipziger Str. 44, Bldg. 64, 39120 Magdeburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Krohn
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000544:Alzheimer Disease / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism*; D002831:Choroid Plexus / Q000378:metabolism; D006801:Humans; D051379:Mice; D049268:Positron-Emission Tomography
chemical_list: D018528:ATP-Binding Cassette Transporters; D016229:Amyloid beta-Peptides
keywords: ABC transporter; ABCA7; ABCB1; ABCC1; Alzheimer’s disease; Amyloid-beta; BBB; Blood–brain barrier; Choroid plexus; Glymphatic system; Neurodegeneration; PET
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