Periodontal Hastalıkların Alzheimer Hastalığı Üzerine Etkileri: Literatür Taraması

Abstract

Beynin nörodejeneratif bir hastalığı olan Alzheimer Hastalığı (AH) ile diş yüzeyine tutunan bakterilerin sebep olduğu lokal inflamatuar bir hastalık olan periodontitis arasında ilişkiyi gösteren çalışmaların sayısı giderek artmaktadır. Klinik bulguları birbirinden tamamen farklı olan bu iki hastalığın gelişim sürecinde inflamasyonun anahtar rol aldığı bilinmektedir. Periodontitis, sistemik dolaşımdaki proinflamatuar sitokinlerin ve C-reaktif protein seviyelerinin arttığı göz önüne alındığında, düşük dereceli bir sistemik hastalık olarak da tanımlanabilir. İnflamasyon AH’nın da önemli özelliklerinden biridir ve periodontitisin AH için risk faktörü olabileceği hipotezinin temelini oluşturur. İnflamasyon teorisinde periferal inflamatuar sürecin amiloid birikimini tetiklediği görüşü ileri sürülmüştür. Periodontitis AH’nı farklı mekanizmalarla etkileyebilir. Bu mekanizmalara örnek olarak, a) periodontal patojenlerin beyne direkt invazyonu veya b) periodontal patojenlerin toksik ürünlerinin beyne ulaşması ve bunların toksik etkileri, ya da c) periodontitis kaynaklı proinflamatuar moleküllerin sistemik dolaşımda sub-klinik dozda artması ve beynin bunlara uzun süre maruz kalması, literatürde ileri sürülmüştür. Bu teorilerle uyumlu olarak kilit periodontal patojenlerden biri olan Porphyromonas gingivalis AH’nın beyinlerinde, beyin omurilik sıvısında tespit edilmiştir. Yine farelere bu oral patojen verildiğinde beyine ulaştığı, AH’nın patolojik belirtileri olan nöroinflamasyon, amiloid plak oluşumu ve nörofibriler demetlerin ortaya çıkmasına sebep olduğu gözlemlenmiştir. Ayrıca AH olan bireylerin beyin dokularında bu patojenin virülans faktörü olan gingipainin arttığı gösterilmiştir. Farede gingipain inhibitörlerinin kullanılmasının enfeksiyonu hafiflettiği, Amyloid beta 42 (Aβ42) peptid birikimini ve nöroinflamasyonu azalttığı gösterilmiştir. Bu derlemenin amacı periodontitis ve AH arasındaki bağlantıyı gözden geçirerek her iki hastalık arasındaki ilişkiyi açıklayan en güncel kanıtları sunmaktır.

Keywords

• Alzheimer hastalığı,
• Periodontitis,
• İnflamasyon,
• P. gingivalis

The Impact of Periodontal Diseases on Alzheimer's Disease: A Literature Review

Abstract

Mounting evidence supports the link between Alzheimer's disease (AD), a neurodegenerative disease of the brain, and periodontitis, an inflammatory disease caused by bacteria attached to the tooth surface. It known that inflammation plays a vital role in the pathogenesis of both diseases with totally different clinical symptoms. Periodontitis can be defined as a low-grade systemic disease, considering that the level of pro-inflammatory cytokines and C-Reaktif protein in the systemic circulation is increased. Inflammation is also one of the important features of AD and forms the basis of the hypothesis that periodontitis may be a risk factor for AD. In inflammation theory, it has been suggested that the peripheral inflammatory process triggers amyloid plaque accumulation. Periodontitis can affect cognitive functions through various mechanisms. The mechanisms proposed in the literature are: a) Direct invasion of microorganism into the brain, b) Toxic products of the periodontal pathogens can reach the brain and have a toxic effect, c) the increase in subclinical doses of pro-inflammatory molecules in the systemic circulation during the host response to periodontitis and the long-term exposure of the brain to these molecules due to the chronic nature of periodontitis. Consistent with these theories, one of the major periodontal pathogens, Porphyromonas. gingivalis, has been detected in AD brains and cerebrospinal fluid. When administered orally to mice, P. gingivalis travels to the brain and induces neuroinflammation, amyloid plaque formation, and neurofibrillary tangles, which are pathological hallmarks of AD. The virulence factor of this pathogen, gingipain, has been shown to be elevated in the brain tissue of people with AD. Interestingly, the use of gingipain inhibitors, a P. gingivalis proteinase, in mice alleviates infection, decreases Amyloid beta 42 (Aβ42) peptide accumulation and neuroinflammation. The purpose of this review is to evaluate the link between periodontitis and AD and present the latest evidence explaining the relationship between both diseases.

Keywords

• Alzheimer's Disease
• Periodontitis
• Inflammation
• P. gingivalis

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