The role of neurovascular unit in pathogenesis of Alzheimer's disease

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09248
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: Oita University
• Principal Investigator: Kimura Noriyuki 大分大学, 医学部, 准教授 (30433048)
• Co-Investigator(Kenkyū-buntansha): 花岡 拓哉 大分大学, 医学部, 講師 (40433057) ; 麻生 泰弘 大分大学, 医学部, 助教 (80555194)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: Neurovascular unit / Alzheimer’s disease / MCI / MRI / PIB-PET / FDG-PET / Blood-brain barrier / Biomarker

Outline of Final Research Achievements

White matter lesions are associated with vascular risk factors, especially hypertension. These lesions affect cognitive function and brain function in patients with Alzheimer's disease at the early stage of disease. Amyloid-positive MCI subjects with cerebral white matter lesions showed increased MMP2, 8, 9, and fibrinogen as well as plasminogen and decreased TIMPs 1 and 2 in the plasma, which related to blood-brain barrier (BBB) damage. In addition, they showed increased MMP12 and decreased TIMP4 in cerebrospinal fluid. The severity of cerebral white matter lesions and BBB damage markers do not correlate with cerebral amyloid deposition. Therefore, we speculated that the BBB damage due to arteriosclerosis and chronic inflammation is related to pathogenesis of cerebral white matter lesions in Alzheimer's disease. Moreover, BBB damage and white matter lesions may affect independently the brain function and cognitive function.

Free Research Field

認知症

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー型認知症の前段階であるMCI due to ADでは、生活習慣病によってNeurovascular unit (NVU)の破綻が生じ、虚血性大脳白質変性が生じていることが推測された。さらに、この大脳白質病変は、前頭葉機能および認知機能障害の進行に影響することが明らかとなった。この研究成果により、NVUの関連分子が症状進行のバイオマーカーだけでなく、新規治療薬のターゲットとなる可能性が示された。従って、本研究はNVU protectionによる脳保護療法という新たな予防法の開発に繋がる。