Neurobiological Effects of Lipoid Proteinosis: A Study on Phosphorylated Tau, S100B, NSE, NEFL, and GFAP

Öz

Background: Lipoid Proteinosis (LP), also termed Urbach-Wiethe disease, is an enigmatic genodermato-sis marked by the systemic deposition of hyaline material. With its etiology rooted in ECM1 mutations, LP’s neuropathological spectrum has been hypothesized to involve an array of neurodegenerative biomarkers, underscoring a potential for substantial neurobiological implications. This study endeav-ored to elucidate the serum concentrations of neurodegenerative biomarkers—phosphorylated Tau (pMAPT), S100B, Neuron-Specific Enolase (NSE), Neurofilament Light Chain (NEFL), and Glial Fibrillary Acidic Protein (GFAP)—in LP patients, seeking to establish their diagnostic utility for the condition. Materials and Methods: Fifteen LP patients and 15 matched healthy controls were enrolled. Serum levels of the biomarkers were quantified using ELISA, and their predictive power was assessed through binary logistic regression and Receiver Operating Characteristic (ROC) analysis. Results: Elevated serum levels of NSE, NEFL, and GFAP were observed in LP subjects relative to healthy counterparts, reaching statistical significance (p<0.05). In contrast, pMAPT and S100B levels did not differ appreciably. GFAP is considered a predictive marker for LP with an area under the curve (AUC) value of 0.813 and a 95% confidence interval (CI) of 0.658-0.968 (p=0.003). Conclusions: The study underscores a distinctive neurodegenerative profile in LP, with NSE, NEFL, and GFAP concentrations significantly amplified. These biomarkers, particularly GFAP, may represent novel indicators for LP, offering prospective biomarker-based diagnostic strategies. The insights garnered herein pave the way for advanced understanding and clinical management of LP, delineating a novel avenue for future high-impact research.

Anahtar Kelimeler

• Lipoid Proteinosis
• Neurodegeneration
• Biomarkers
• Diagnostic Neurology
• ECM1

Etik Beyan

The study protocol adhered to the ethical standards established by the Declaration of Helsinki and Good Clinical Practice guidelines, and received approval from the Clinical Research Ethics Committee of Harran University (HRU/23.24.26).

Lipoid Proteinozisin Nörobiyolojik Etkileri: Fosforile Tau, S100B, NSE, NEFL ve GFAP Üzerine Bir Araştırma

Öz

Amaç: Urbach-Wiethe hastalığı olarak da adlandırılan Lipoid Proteinozis (LP), hiyalin materyalinin sistemik olarak birikmesiyle belirginleşen bir genodermatozdur. Etiyolojisi ECM1 mutasyonlarına da-yanan LP'nin nöropatolojik spektrumunun, önemli nörobiyolojik etkilerin potansiyelinin altını çizen bir dizi nörodejeneratif biyobelirteç içerdiği varsayılmıştır. Bu çalışma, LP hastalarında nörodejeneratif biyobelirteçlerin (fosforile Tau (pMAPT) S100B, Nöron Spesifik Enolaz (NSE), Nörofilament Hafif Zincir (NEFL) ve Glial Fibriller Asidik Protein (GFAP) ) serum konsantrasyonlarını ölçmeyi ve bu belirteçlerin tanısal potasiyellerini belirlemeyi amaçladı. Materyal ve Metod: 15 LP'li hasta ve 15 sağlıklı kontrol çalışmaya dahil edildi. Nörodejeneratif biyobe-lirteçlerin serum seviyeleri ELISA testleri kullanılarak ölçüldü ve prediktif güçleri ikili lojistik regresyon ve Receiver Operating Characteristic (ROC) analizi yoluyla değerlendirildi. Bulgular: LP hastalarında sağlıklı kontrollere göre NSE, NEFL ve GFAP serum düzeyleri daha yüksekti ve bu artışın istatistiksel olarak anlamlı olduğu bulundu (p<0.05). Buna karşılık, pMAPT ve S100B seviyele-rinde anlamlı farklılık gözlenmedi. GFAP'nin, 0.813'lük eğri altında kalan alan (AUC) değeri ve 0.658-0.968'lik %95 güven aralığı (CI) ile LP için prediktif bir belirteç olabileceği düşünülmektedir (p=0.003). Sonuç: Bu sonuçlar NSE, NEFL ve GFAP konsantrasyonlarının LP’de önemli ölçüde arttığını göstermekte ve LP'de belirgin bir nörodejeneratif profilin altını çizmektedir. Bu biyobelirteçler, özellikle GFAP, LP için yeni bir indikatör olabilir ve ileriye yönelik biyobelirteç bazlı tanı stratejileri sunabilir. Bu çalış-mada elde edilen bilgiler, gelecekteki yüksek etkili araştırmalar için yeni bir yol çizerek LP'nin anlaşıl-ması ve klinik yönetiminde yol gösterici olacaktır.

Anahtar Kelimeler

• Lipoid Proteinozis
• Nörodejenerasyon
• Biyobelirteçler
• Tanısal Nöroloji
• ECM1

Kaynakça

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