www.neurologiepropraxi.cz / Neurol. praxi. 2025;26(1):17-23 / NEUROLOGIE PRO PRAXI 23 HLAVNÍ TÉMA Genetika Alzheimerovej choroby a demencie s Lewyho telieskami Praktické odporúčania genetického testovania vo vzťahu k antiamyloidnej terapii Monoklonálne protilátky proti beta amyloidu (lecanemab a donanemab) otvárajú novú éru v terapii Alzheimerovej choroby. Napriek množstvu kontroverzií, s ktorými sú spojené, predstavujú zásadný míľnik, ktorý má celospoločenský presah. Genetické testovanie APOE genotypu bude mandatórnou podmienkou indikovania liečby. V prípade lecanemabu je liek indikovaný u ApoE4 nenositeľov a ApoE4 heterozygotov. ApoE4 homozygoti by mali byť z liečby vylúčení pre vysoké riziko ARIA fenoménu. V prípade donanemabu sa uvažuje o vylúčení akýchkoľvek nositeľov ε4 alely, takže je možné, že bude indikovaný len pre relatívne úzku kohortu pacientov. Každopádne genetické testovanie APOE genotypu bude musieť byť dostupné v každom centre, ktoré bude indikovať liečbu. Záver Alzheimerova choroba a demencia s Lewyho telieskami sú dve najfrekventovanejšie neurodegeneratívne demencie. Sú to prekrývajúce sa množiny, pričom platí, že čím viac patológií v mozgu konkomitantne prebieha, tým je klinický priebeh rýchlejší. Každá z týchto demencií má svoje špecifické genetické pozadie, pričom niektoré gény sú vysoko špecifické pre dané ochorenie, iné sú zdieľané medzi obomi entitami. Je predpoklad, že v budúcnosti sa na základe vedomostí z GWAS a MPS (massive paralel sequencing) rozšíri repertoár génov zapojených do patogenézy oboch neurodegeneratívnych demencií. Význam genetiky nespočíva len v identifikácii príčiny ochorenia, ale stáva sa podkladom na triedenie pacientov na špecifickú terapiu. Napríklad lecanemab aj donanemab (monoklonálne protilátky na liečbu AD), ako už bolo spomenuté, sa ukazujú ako nevhodné pre ApoE4/4 homozygotov. 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