핵의학

본문글자크기
  • [Brain.] Microglial activation correlates in vivo with both tau and amyloid in Alzheimer's disease.

    Hammersmith Hospital / Dani M*

  • 출처
    Brain.
  • 등재일
    2018 Sep 1
  • 저널이슈번호
    141(9):2740-2754. doi: 10.1093/brain/awy188.
  • 내용

    바로가기  >

    Abstract
    Alzheimer's disease is characterized by the histopathological presence of amyloid-β plaques and tau-containing neurofibrillary tangles. Microglial activation is also a recognized pathological component. The relationship between microglial activation and protein aggregation is still debated. We investigated the relationship between amyloid plaques, tau tangles and activated microglia using PET imaging. Fifty-one subjects (19 healthy controls, 16 mild cognitive impairment and 16 Alzheimer's disease subjects) participated in the study. All subjects had neuropsychometric testing, MRI, amyloid (18F-flutemetamol), and microglial (11C-PBR28) PET. All subjects with mild cognitive impairment and Alzheimer's disease and eight of the controls had tau (18F-AV1451) PET. 11C-PBR28 PET was analysed using Logan graphical analysis with an arterial plasma input function, while 18F-flutemetamol and 18F-AV1451 PET were analysed as target:cerebellar ratios to create parametric standardized uptake value ratio maps. Biological parametric mapping in the Statistical Parametric Mapping platform was used to examine correlations between uptake of tracers at a voxel-level. There were significant widespread clusters of positive correlation between levels of microglial activation and tau aggregation in both the mild cognitive impairment (amyloid-positive and amyloid-negative) and Alzheimer's disease subjects. The correlations were stronger in Alzheimer's disease than in mild cognitive impairment, suggesting that these pathologies increase together as disease progresses. Levels of microglial activation and amyloid deposition were also correlated, although in a different spatial distribution; correlations were stronger in mild cognitive impairment than Alzheimer's subjects, in line with a plateauing of amyloid load with disease progression. Clusters of positive correlations between microglial activation and protein aggregation often targeted similar areas of association cortex, indicating that all three processes are present in specific vulnerable brain areas. For the first time using PET imaging, we show that microglial activation can correlate with both tau aggregation and amyloid deposition. This confirms the complex relationship between these processes. These results suggest that preventative treatment for Alzheimer's disease should target all three processes.

     


    Author information

    Dani M1, Wood M1, Mizoguchi R1, Fan Z1, Walker Z2,3, Morgan R4, Hinz R5, Biju M6, Kuruvilla T6, Brooks DJ1,7,8, Edison P1.
    1
    Neurology Imaging Unit, Department of Medicine, Imperial College London, Hammersmith Hospital, UK.
    2
    Division of Psychiatry, University College London, UK.
    3
    Essex Partnership University NHS Foundation Trust, UK.
    4
    Chelsea and Westminster Hospital, London, UK.
    5
    Wolfson Molecular Imaging Centre, University of Manchester, UK.
    6
    Gether NHS Foundation Trust, Gloucester, UK.
    7
    Department of Nuclear Medicine, Aarhus University, Denmark.
    8
    Institute of Neuroscience, University of Newcastle upon Tyne, UK.

  • 편집위원

    tau, amyloid 그리고 PBR28을 통한 microglia imaging을 모두 시행하여 image기반의 연관성을 본 연구로, microglia가 amyloid deposit과 tau 증가에 대해 spatial하게 어떤 관계를 가지고 있는지 살펴본 연구로, 추후 어떤 imaging biomarker를 써야할지, 어떤 것을 target으로 Alzheimer치료에 접근할 지 고민해볼 수 있게 수행한 연구입니다.

    2018-10-23 12:15:08

  • 덧글달기
    덧글달기
       IP : 54.166.170.195

    등록