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Journals / Akdeniz Tıp Dergisi / 2026 / Cilt: 12 Sayı: 1

New Neuropathological Definitions in Late-Life Dementias

Geç Yaş Demanslarında Yeni Nöropatolojik Tanımlar

Özlem Totuk(SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, İSTANBUL SANCAKTEPE ŞEHİR PROF. DR. İLHAN VARANK SAĞLIK UYGULAMA VE ARAŞTIRMA MERKEZİ, DAHİLİ TIP BİLİMLERİ BÖLÜMÜ, NÖROLOJİ ANABİLİM DALI)0000-0001-7274-025X
Şevki Sahin(SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, İSTANBUL SANCAKTEPE ŞEHİR PROF. DR. İLHAN VARANK SAĞLIK UYGULAMA VE ARAŞTIRMA MERKEZİ, DAHİLİ TIP BİLİMLERİ BÖLÜMÜ, NÖROLOJİ ANABİLİM DALI)0000-0003-2016-9965
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Publication Date
2026-04-16
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

In the future, a better understanding of the pathophysiology of these disorders may enhance diagnostic accuracy and contribute to the development of personalized therapeutic strategies.

📌 3 Key Takeaways

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Objective & Hypothesis:ABSTRACT Neurodegenerative diseases are a heterogeneous group of disorders that increase in incidence with aging and lead to progressive cognitive decline.
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Key Findings & Data:In this context, pathological entities such as Limbic-Predominant Age-Related TDP-43 Encephalopathy (LATE), Primary Age-Related Tauopathy (PART), Aging-Related Tau Astrogliopathy (ARTAG), Argyrophilic Grain Disease (AGD), and Globular Glial Tauopathy (GGT) have been identified as distinct components of the dementia spectrum.
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Conclusion & Impact:In the future, a better understanding of the pathophysiology of these disorders may enhance diagnostic accuracy and contribute to the development of personalized therapeutic strategies.
🔬Design:Review & Systematic Survey
📍Scope:Comprehensive Sample
⚙️Variables:Nörodejenerasyon · Demans · İleri yaş

Abstract

ABSTRACT Neurodegenerative diseases are a heterogeneous group of disorders that increase in incidence with aging and lead to progressive cognitive decline. While Alzheimer’s disease (AD) is recognized as the most common neurodegenerative disorder, recent years have seen the emergence of newly defined conditions that exhibit similar clinical symptoms but are driven by distinct pathological mechanisms. In this context, pathological entities such as Limbic-Predominant Age-Related TDP-43 Encephalopathy (LATE), Primary Age-Related Tauopathy (PART), Aging-Related Tau Astrogliopathy (ARTAG), Argyrophilic Grain Disease (AGD), and Globular Glial Tauopathy (GGT) have been identified as distinct components of the dementia spectrum. Although these diseases share overlapping clinical features with AD, they are characterized by different patterns of protein accumulation. LATE is primarily associated with the accumulation of TDP-43 protein, whereas PART and AGD are classified as Tau proteinopathies. GGT, on the other hand, is distinguished by the predominant accumulation of Tau within glial cells. From a neuropathological perspective, distinguishing these conditions from AD is challenging, and it has been reported that Tauopathies lacking amyloid deposition, such as LATE and PART, are frequently overlooked. Additionally, the high rate of misdiagnosis in AD further complicates the diagnostic evaluation of these neurodegenerative processes. According to the current literature, the definitive diagnosis of these conditions is only possible through postmortem neuropathological examinations. However, the development of biomarkers and the application of advanced imaging techniques may facilitate early diagnosis and enable their differentiation from AD. This review explores the newly recognized neuropathological processes associated with age-related memory impairment, providing a comprehensive discussion on their neuropathological characteristics, comparative analysis with AD, and current diagnostic approaches. In the future, a better understanding of the pathophysiology of these disorders may enhance diagnostic accuracy and contribute to the development of personalized therapeutic strategies.

Özet

ÖZ Nörodejeneratif hastalıklar, yaşlanmayla birlikte insidansı artan ve ilerleyici bilişsel işlev kaybına neden olan heterojen bir hastalık grubudur. Alzheimer demans (AD), en yaygın nörodejeneratif hastalık olarak bilinmekle birlikte, ileri yaş başlangıçlılarda son yıllarda benzer klinik semptomlarla seyreden ancak farklı patolojik mekanizmalara sahip yeni tanımlamalar ortaya konmuştur. Bu bağlamda, Limbik-Baskın Yaşla-İlintili TDP-43 Ensefalopatisi (LATE - Limbic-Predominant Age-Related TDP-43 Encephalopathy), Primer yaş-ilintili Tauopati (PART - Primary Age-Related Tauopathy), Yaşa Bağlı Tau Astrogliopatisi (ARTAG - Aging-Related Tau Astrogliopathy), Arjirofilik Tahıl Hastalığı (AGD - Argyrophilic Grain Disease) ve Globüler Glial Tauopati (GGT - Globular Glial Tauopathy) gibi patolojiler demans spektrumu içinde ayrı bir yer edinmiştir. Bu hastalıklar, AD ile örtüşen klinik semptomlar göstermekle birlikte, farklı protein birikimleriyle karakterizedir. LATE, öncelikli olarak TDP-43 protein birikimi ile tanımlanırken; PART ve AGD Tau proteinopatileri olarak kabul edilir. GGT ise glial hücrelerde yoğunlaşan Tau birikimi ile ayırt edilir. Nöropatolojik açıdan bakıldığında, bu hastalıkların AD’den ayrımı güç olup, özellikle amiloid-negatif Tauopatiler olan LATE ve PART’in yaygın olarak gözden kaçtığı bildirilmektedir. Yanı sıra, AD'nin yüksek yanlış tanı oranı, bu nörodejeneratif süreçlerin tanısal değerlendirmelerinde ek zorluklar yaratmaktadır. Güncel literatürde, bu hastalıkların kesin tanısı yalnızca postmortem nöropatolojik incelemelerle mümkün olabilmektedir. Bununla birlikte, biyobelirteçlerin geliştirilmesi ve ileri görüntüleme tekniklerinin kullanımı, bu hastalıkların erken teşhis edilmesine ve AD’den ayırıcı tanısının yapılmasına olanak tanıyabilir. Bu derleme, ileri yaşta bellek bozukluğu ile ilişkili yeni tanımlanmış nöropatolojik süreçleri ele almakta; bu hastalıkların nöropatolojik özelliklerini, AD ile karşılaştırmalı analizlerini ve mevcut tanısal yaklaşımlarını kapsamlı bir şekilde tartışmaktadır. Gelecekte, bu hastalıkların patofizyolojisinin daha iyi anlaşılması, tanısal doğruluğun artırılmasını sağlayarak bireyselleştirilmiş tedavi yaklaşımlarının geliştirilmesine katkıda bulunabilir.

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Cite This Article

Totuk, Ö., Sahin, Ş. (2026). New Neuropathological Definitions in Late-Life Dementias. Akdeniz Tıp Dergisi, Cilt: 12 Sayı: 1. https://doi.org/10.53394/akd.1652178

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