Pathology-specific propagation mechanisms revealed by analysis of alpha-synuclein in blood

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K16928
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Juntendo University
• Principal Investigator: Okuzumi Ayami 順天堂大学, 医学部, 准教授 (90826075)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: パーキンソン病 / αシヌクレイン / 多系統萎縮症

Outline of Final Research Achievements

Parkinson’s disease (PD) and Multiple system atrophy (MSA) are synucleinopathies, comprising pathomechanisms that involve alpha-synuclein (aSyn) seeds converting a native form of aSyn into abnormal conformational structures with propagative properties. Although aSyn seeds are detected in various tissues, it remains unclear whether these seeds exist in the serum. IP/RT-QuIC enables the detection of serum pathogenic aSyn seeds and proves a useful diagnostic biomarker for synucleinopathy. Furthermore, the amplified aSyn seeds maintain their disease-specific morphological and propagative properties. Finally, this novel approach also allows the distinction between PD and MSA.

Free Research Field

Neurology

Academic Significance and Societal Importance of the Research Achievements

α-シヌクレイノパチー患者の血液中に存在するα-シヌクレインシードがα-シヌクレイノパチーの診断と鑑別のマーカーとして有用であることを明らかにした。また、増幅された血清α-シヌクレインシードは伝播能を保持し、さらには、疾患毎に構造の異なる凝集体を形成することが分かった。今後は血液を用いた簡便かつ有用な診断方法の確立を目指すとともに、疾患ごとの凝集体構造の相違などに着目することで、病態解明をめざす。