Eisen im alternden Gehirn

Zusammenfassung

Eisen ist ein essentielles Spurenelement für eine Vielzahl von Stoffwechselreaktionen des Körpers. Auch im Gehirn ist es von besonderer Bedeutung. Die Aufnahme über die Blut-Hirn-Schranke und die Verteilung und Speicherung im Gehirn ist ein streng regulierter Prozess, damit neurotoxische Effekte des Eisens verhindert werden. Im alternden Gehirn geht vermehrte Eisenspeicherung in Kortex und Basalganglien mit Einschränkungen der kognitiven und motorischen Fähigkeiten einher. Man geht außerdem davon aus, dass Eisen zu neurodegenerativen Erkrankungen des Alters wie Morbus Parkinson und Morbus Alzheimer beiträgt. Vermehrte Eisenablagerung findet sich beim Morbus Parkinson in der Substantia nigra, wo dopaminerge Neurone untergehen. Eisen fördert außerdem die α-Synuclein-Aggregation in Lewy-Körperchen und sorgt für Bildung toxischer Hydroxylradikale. Beim Morbus Alzheimer ist Eisen an der Bildung von β-Amyloid-Plaques und Neurofibrillen-Bündeln beteiligt. Eine verminderte Ferroxidase-Aktivität des Amyloid-Vorläuferproteins trägt zu erhöhter zerebraler Eisenakkumulation bei. Die Liquor-Ferritinspiegel bei Trägern des Alzheimer-Risikoallels ApoE4 sind erhöht. Klinisch sind die Eisenspiegel in Basalganglien und Hippocampi negativ mit kognitiven Leistungen assoziiert. Gleichzeitig sind erhöhte Liquor-Ferritinspiegel mit früherem Krankheitsbeginn assoziiert. Schließlich betont die pathologische zerebrale Eisenakkumulation bei allen Subformen der Neurodegeneration mit Eisenablagerung (neurodegeneration with brain iron accumulation, NBIA) die Bedeutung des Eisens für neurodegenerative Erkrankungen.

Abstract

Iron as an essential trace element is a major contributor to many metabolic pathways in the body and the brain. The transfer of iron through the blood-brain barrier and the distribution and storage in the brain is tightly regulated in order to prevent neurotoxicity. Increased iron levels in the ageing brain in cortex and basal ganglia lead to impaired cognitive and motor functions. Moreover, iron contributes to neurodegenerative diseases in the elderly such as Parkinson’s and Alzheimer’s disease. Increased iron deposition in Parkinson’s disease can be found in the substantia nigra where substantial neuronal loss occurs. Iron also promotes aggregation of α-synuclein in Lewy bodies and production of toxic hydroxyl radicals. In Alzheimer’s disease, iron participates in the generation of β-amyloid plaques and neurofibrillary tangles. Vice versa, reduced ferroxidase activity of the amyloid precursor protein contributes to increased cerebral iron accumulation. Ferritin levels in the cerebrospinal fluid (CSF) are increased in patients with the APOE4 allele, a risk factor for Alzheimer’s disease. Clinically, iron levels of the basal ganglia and the hippocampi are negatively associated with cognitive performances. Furthermore, increased CSF ferritin levels are associated with earlier disease onset. Last but not least, the pathological cerebral iron accumulation in the group of disorders called neurodegeneration with brain iron accumulation (NBIA) emphasizes the important role of iron in neurodegenerative diseases.

Schlüsselwörter

Eisen - Altern - Gehirn - Neurodegeneration

Keywords

iron - ageing - brain - neurodegeneration

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