Entorhinal vessel density correlates with phosphorylated tau and TDP-43 pathology

被引:0
|
作者
Llamas Rodriguez, Josue [1 ]
van der Kouwe, Andre J. W. [1 ]
Oltmer, Jan [1 ,2 ]
Rosenblum, Emma [1 ]
Mercaldo, Nathaniel [3 ,4 ]
Fischl, Bruce [1 ,5 ]
Marshall, Michael [6 ]
Frosch, Matthew P. [6 ]
Augustinack, Jean C. [1 ]
机构
[1] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, 149 Thirteenth St,Suite 2301, Charlestown, MA 02129 USA
[2] Vivantes Netzwerk Gesundheit GmbH, Dept Digital Hlth & Innovat, Berlin, Germany
[3] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA
[4] Massachusetts Gen Hosp, MGH Inst Technol Assessment, Boston, MA USA
[5] MIT, CSAIL, Cambridge, MA USA
[6] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA USA
基金
美国国家卫生研究院;
关键词
intracortical; parahippocampal gyrus; perirhinal cortex; proximity; subfields; vasculature; ALZHEIMERS-DISEASE; NEUROFIBRILLARY TANGLES; COGNITIVE IMPAIRMENT; CORTEX; MICROGLIA; MICROVASCULATURE; NEUROPATHOLOGY; ABNORMALITIES; ACCUMULATION; INFLAMMATION;
D O I
10.1002/alz.13896
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
INTRODUCTIONThe entorhinal cortex (EC) and perirhinal cortex (PC) are vulnerable to Alzheimer's disease. A triggering factor may be the interaction of vascular dysfunction and tau pathology.METHODSWe imaged post mortem human tissue at 100 mu m3 with 7 T magnetic resonance imaging and manually labeled individual blood vessels (mean = 270 slices/case). Vessel density was quantified and compared per EC subfield, between EC and PC, and in relation to tau and TAR DNA-binding protein 43 (TDP-43) semiquantitative scores.RESULTSPC was more vascularized than EC and vessel densities were higher in posterior EC subfields. Tau and TDP-43 strongly correlated with vasculature density and subregions with severe tau at the preclinical stage had significantly greater vessel density than those with low tau burden.DISCUSSIONThese data impact cerebrovascular maps, quantification of subfield vasculature, and correlation of vasculature and pathology at early stages. The ordered association of vessel density, and tau or TDP-43 pathology, may be exploited in a predictive context.Highlights Vessel density correlates with phosphorylated tau (p-tau) burden in entorhinal and perirhinal cortices. Perirhinal area 35 and posterior entorhinal cortex showed greatest p-tau burden but also the highest vessel density in the preclinical phase of Alzheimer's disease. We combined an ex vivo magnetic resonance imaging model and histopathology to demonstrate the 3D reconstruction of intracortical vessels and its spatial relationship to the pathology.
引用
收藏
页码:4649 / 4662
页数:14
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