Significance and clinical application of GDF15 in mitochondrial dysfunction in Alzheimer's disease

2022 Fiscal Year Final Research Report

• Project/Area Number: 17K15887
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: University of Tsukuba
• Principal Investigator: Tsuji Hiroshi 筑波大学, 医学医療系, 講師 (40633970)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Keywords: GDF15

Outline of Final Research Achievements

A secreted protein called GDF15 (Growth/differentiation factor 15) reflects mitochondrial function. Elucidating the dynamics of GDF15 in biological samples may clarify AD and mitochondrial dysfunction. We, therefore, measured and compared GDF15 levels in cerebrospinal fluid in multiple sclerosis (MS), central nervous system lymphoma (CNS lymphoma), and glioma. The cerebrospinal fluid GDF15 values of 9 patients with multiple sclerosis, 6 patients with CNS lymphoma, and 3 patients with glioblastoma were 320.4±246.5 pg/ml, 419.5±237.6 pg/ml, and 471.0±237.6 pg/ml, respectively. The values were significantly higher in CNS lymphoma and glioma compared with MS (P ＝ 0.009, P = 0.037). Based on the above results, GDF15 is useful in distinguishing between MS and malignant diseases of the central nervous system. These results show that GDF15 can be measured in clinical samples and used for neurodegenerative diseases such as Alzheimer’s disease.

Free Research Field

神経内科

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー型認知症は，高齢化社会と共に罹患者数が増加傾向にあり，社会問題となっている．アルツハイマー病の原因にアミロイドβ蛋白が，疾患感受性遺伝子にアポリポ蛋白Eのアイソフォームが関わってくる．これらの蛋白は神経細胞内の酸化ストレスに影響され，その細胞内の酸化を担うのがミトコンドリアである．最近，ミトコンドリア機能異常がアルツハイマー病の発症と関係があることが報告されており，またミトコンドリア機能を反映するのが，GDF15という分泌性蛋白である．本研究ではGDF15を髄液で測定できることが明らかとなり、臨床応用が可能となった。