The in vivo quantification of iron deposition in the brain and its relation to pathological hallmarks of Alzheimer’s disease

Eva Wachtelaer
De ziekte van Alzheimer blijft een uitdaging voor hersenspecialisten over de hele wereld. Een recente vondst stelt voor dat afwijkende ijzerwaarden in de hersenen kunnen bijdragen aan het ontstaan en de progressie van deze ziekte. In deze thesis worden de ijzerwaarden van 180 deelnemers, inclusief gezonde personen en patiënten, onderzocht.

Hoe roest in de hersenen kan leiden tot de ziekte van Alzheimer

Neen hoor, in deze titel is geen beeldspraak gebruikt. Net zoals metaal, kunnen onze hersenen roesten. Dit leidt tot beschadiging van de hersenen en wordt ervan verdacht een belangrijke oorzaak van Alzheimer te zijn.

 

De ziekte van Alzheimer blijft een uitdaging voor hersenspecialisten over de hele wereld. Bij de patiënten van deze ziekte verdwijnen stukjes van hun hersenen, waardoor ze problemen krijgen met hun geheugen, taal, emoties en nog veel meer. Hoe deze ziekte ontstaat en precies in zijn werk gaat, blijft een mysterie. Als gevolg zijn er ook nog geen behandelingen beschikbaar. Dit is een groot probleem, aangezien elke vier seconden iemand Alzheimer krijgt en dit blijft toenemen!

Onderzoekers zijn volop bezig met het ontrafelen van de mysteries rond deze ziekte en zeer recent werd een interessante vondst gedaan. IJzer in de hersenen zou namelijk een belangrijke rol kunnen spelen bij het ontstaan van Alzheimer (Figuur 1).

image-20191005161339-4
Figuur 1. Figuratieve voorstelling van roest in de hersenen.

Hoe kan ijzer Alzheimer veroorzaken?

Iedereen kent ijzer als het veelvoorkomende metaal op Aarde. Het heeft uiteenlopende toepassingen, denk maar aan ijzeren schroeven, stalen bestek en het ijzer gebruikt om fietsen en auto’s te maken. IJzer komt hiernaast ook veel voor in het menselijk lichaam. Het speelt in het lichaam een belangrijke rol in onder andere het voorzien van organen van zuurstof en in de vorming van zenuwen. Deze laatste zijn belangrijk voor de communicatie tussen hersencellen onderling en met de rest van het lichaam.

Hoewel ijzer essentieel is voor ons lichaam, en specifieker, de hersenen, kan het ook enorme schade aanrichten. Het is namelijk belangrijk dat de hoeveelheid ijzer in de hersenen strikt gecontroleerd wordt.

In het geval van te weinig ijzer, kan het zijn belangrijke taken niet uitvoeren. Dit leidt onder andere tot zuurstoftekort in de hersencellen, waardoor deze afsterven. Daarnaast kunnen de zenuwen hun taken niet meer uitvoeren, waardoor de verschillende hersencellen niet meer kunnen samenwerken.
Een te hoge hoeveelheid aan ijzer in de hersenen is ook gevaarlijk. Het teveel aan ijzer werkt in op de hersencellen, waardoor deze uiteindelijk afsterven. Dit fenomeen kan vergeleken worden met het roesten van metaal. Hoewel de chemische reacties niet volledig overeenkomen, vereisen beide de aanwezigheid van zuurstof en water. Bij deze reacties worden hydroxide ionen geproduceerd die schade kunnen berokkenen aan zowel metaal als aan de hersenen. Het resultaat hiervan is het ontstaan van roest, met als gevolg verzwakking van het metaal/orgaan en uiteindelijk het optreden van gaten (Figuur 2).

Aangezien beide situaties leiden tot het afsterven van delen van de hersenen, kan ijzer een rol spelen in het ontstaan van Alzheimer. Net zoals het roesten van metalen, is dit een langzaam, maar rampzalig proces.

image-20191005161607-5
Figuur 2. Bij Alzheimer patiënten verdwijnen stukjes van de hersenen, waardoor gaten ontstaan.

Hoe kan ijzer in de hersenen gemeten worden?

De hoeveelheid ijzer in de hersenen meten is een volgende uitdaging voor onderzoekers. De meerderheid van de mensen heeft zijn bloed wel eens laten nakijken, waarbij de hoeveelheid ijzer ook nagekeken werd. De hoeveelheid ijzer in het bloed is echter niet gelijk aan de hoeveelheid in de hersenen. Bovendien wordt ijzer in het bloed heel gemakkelijk verzameld via een prikje in de arm,  maar zijn de hersenen moeilijker bereikbaar omdat deze door een stevige schedel omgeven worden.

De methode toegepast tijdens dit thesisonderzoek maakte gebruik van een beeldvormingstechniek, ‘magnetic resonance imaging’ of ‘MRI’ genoemd (Figuur 3). Deze techniek gebruikt een hersenscanner die opgebouwd is uit magneten die helpen bij het vormen van beelden van de hersenen. Aangezien ijzer magnetische eigenschappen bezit, is dit een ideale techniek om het ijzer in de hersenen in beeld te brengen. Deze techniek is zelfs zo gevoelig dat de concentratie van ijzer in de verschillende hersendelen gemeten kan worden!

image-20191005161724-6
Figuur 3. Voorstelling van een MRI-scanner. De patiënt gaat op de witte onderzoekstafel liggen, die hierna in de cilinder geschoven wordt.

Hoe verschilt ijzer bij Alzheimer patiënten?

Voor deze thesis zijn de MRI beelden van 180 mensen onderzocht, inclusief gezonde jongvolwassenen, gezonde bejaarden en bejaarden met Alzheimer. Bij het vergelijken van de ijzerwaarden tussen gezonde jongeren en ouderen, bleek dat de waarden afweken op hogere leeftijd. Deze afwijkingen zouden gelinkt kunnen worden aan de typische achteruitgang van het geheugen in gezonde ouderen.
Bij patiënten met Alzheimer waren de afwijkingen in ijzerwaarden nog veel opvallender. Zowel te lage als te hoge waarden werden teruggevonden. Dit bevestigt de veronderstelling dat beide kunnen bijdragen aan beschadiging van de hersenen.

Dé oplossing voor Alzheimer?

Jammer genoeg is er tot nu toe onvoldoende onderzoek verricht om zeker te zijn dat afwijkende ijzerwaarden Alzheimer veroorzaken. Niettemin moedigen de interessante resultaten onderzoekers aan om verder in te gaan op dit onderwerp.
Indien de rol van ijzer in de ziekte van Alzheimer bevestigd kan worden, opent dit nieuwe deuren voor mogelijke behandelingen van de ziekte. Bij te lage concentraties van ijzer kunnen simpelweg ijzersupplementen voorgeschreven worden voor de patiënt. Bij te hoge concentraties kunnen geneesmiddelen voorgeschreven worden die het ijzer uit het lichaam verwijderen, ijzer chelators genoemd. Beide geneesmiddelen zijn gemakkelijk toe te dienen en veroorzaken weinig tot geen bijwerkingen. Dit zou een fantastische doorbraak zijn voor de Alzheimer patiënten.

Conclusie

De ziekte van Alzheimer is een steeds vaker voorkomende ziekte die dodelijk is. Het ontstaan en verloop van de ziekte is nog steeds niet goed begrepen, waardoor er geen behandelingen beschikbaar zijn.
Afwijkende hoeveelheden van ijzer in de hersenen kunnen roest vormen, wat leidt tot het verlies van hersencellen en beschadiging van dit orgaan. Hierdoor kunnen symptomen zoals geheugenverlies ontstaan.

Door de veelbelovende resultaten en verscheidene behandelingsmogelijkheden zijn onderzoekers volop bezig de rol van ijzer in Alzheimer te bestuderen, in de hoop het mysterie van Alzheimer te kunnen ontrafelen.

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Universiteit of Hogeschool
Neurosciences
Publicatiejaar
2019
Promotor(en)
Prof. Dr. Pedro Rosa-Neto and Prof. Dr. Sebastiaan Engelborghs
Kernwoorden
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