Embryological Origins and Genetics in Frontotemporal Dementia

Abstract

Frontotemporal dementia (FTD) represents a heterogeneous group of neurodegenerative disorders marked by progressive deterioration in behavior, language, and executive function. While its genetic architecture dominated by mutations in C9orf72, GRN, and MAPT has been widely studied, less attention has been given to how early neurodevelopmental processes may shape regional vulnerability. This review integrates current findings in molecular genetics with insights from embryonic development of the frontal and temporal lobes. Key signaling pathways such as Wnt, SHH, and Notch are examined in the context of FTD-related pathology. Emphasis is placed on how embryological disruption may predispose cortical regions to later neurodegeneration. The clinical implications of these developmental-genetic interactions are also explored, underscoring their relevance in future biomarker discovery and therapeutic targeting.

Keywords

• embryology
• frontotemporal dementia
• genetics
• molecular pathways
• neurodegeneration

Frontotemporal Demansta Embriyolojik Kökenler ve Genetik

Abstract

Frontotemporal demans (FTD), davranış, dil ve yürütücü işlevlerde ilerleyici bozulma ile seyreden heterojen bir nörodejeneratif bozukluk grubudur. C9orf72, GRN ve MAPT gibi başlıca genetik mutasyonların rolü bilinmekle birlikte, bu genetik zeminin beyin korteksinin önceden programlanmış embriyolojik kırılganlıklarıyla nasıl kesiştiği yeterince açıklığa kavuşmamıştır. Bu derleme, frontal ve temporal lobların erken gelişimsel süreçleri ile FTD’ye özgü genetik mekanizmaları bir araya getirerek, nöronal göç, sinaptogenez ve miyelinizasyon gibi evrelerin hastalık patogenezindeki yerini tartışmaktadır. Sonuç olarak, bu gelişimsel-genetik etkileşimlerin klinik bulgu çeşitliliğini nasıl etkilediği ve yeni biyobelirteç geliştirme çalışmalarına nasıl yön verebileceği değerlendirilmiştir.

Keywords

• embriyoloji
• frontotemporal demans
• genetik
• moleküler yolaklar
• nörodejenerasyon

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