Associations between near end-of-life flortaucipir PET and postmortem CTE-related tau neuropathology in six former American football players.
Associations between near end-of-life flortaucipir PET and postmortem CTE-related tau neuropathology in six former American football players.
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DOI：
10.1007/s00259-022-05963-x
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发表时间：
2023-01
影响因子：
9.1
通讯作者：
Stern, Robert A.
中科院分区：
文献类型：
--
作者：
Alosco, Michael L.;Su, Yi;Stein, Thor D.;Protas, Hillary;Cherry, Jonathan D.;Adler, Charles H.;Balcer, Laura J.;Bernick, Charles;Pulukuri, Surya Vamsi;Abdolmohammadi, Bobak;Coleman, Michael J.;Palmisano, Joseph N.;Tripodis, Yorghos;Mez, Jesse;Rabinovici, Gil D.;Marek, Kenneth L.;Beach, Thomas G.;Johnson, Keith A.;Huber, Bertrand Russell;Koerte, Inga;Lin, Alexander P.;Bouix, Sylvain;Cummings, Jeffrey L.;Shenton, Martha E.;Reiman, Eric M.;McKee, Ann C.;Stern, Robert A.
关键词：
Flourine-18-flotaucipir tau正电子发射断层扫描（PET）被开发用于检测阿尔茨海默病。人类成像研究已经开始调查其在慢性创伤性脑病（CTE）中的应用。诊断确认需要在CTE中进行Flortaucipir-PET与尸检相关性研究。我们研究了6名前美式足球运动员的生命末期flortaucipir PET与CTE相关tau的死后神经病理学测量之间的关联。三名前国家足球联盟球员和三名前大学足球运动员谁是诊断CTE研究项目的一部分死亡，并同意有他们的大脑捐赠。这六名球员在死前接受了flortaucipir（tau）和florbetapir（淀粉样蛋白）PET。对所有死亡参与者的大脑进行神经病理学评估，以确定CTE的存在。平均而言，参与者在PET时的年龄为59.0（SD = 9.32）岁。在他们死亡前20.33（SD = 13.08）个月获得PET扫描。使用斯皮尔曼相关性分析，我们比较了flortaucipir标准摄取值比（SUVR）与基于数字载玻片的AT 8磷酸化tau（p-tau）密度在先验选择的复合皮质、复合边缘和丘脑感兴趣区域（ROI）中的差异。四名脑供体具有尸检确认的CTE，均具有高阶段疾病（n = 3个III期，n = 1个IV期）。这四个中的三个符合CTE临床综合征的标准，称为创伤性脑病综合征（TES）。两个没有CTE尸检，其中一个符合标准的TES。仅在1例非CTE病例（路易体）和1例CTE病例（运动神经元疾病）中存在伴随病理学。复合皮质（ρ = 0.71）和边缘（ρ = 0.77）ROI中flortaucipir SUVR与p-tau密度之间存在强相关性。尽管在丘脑ROI中存在强关联（ρ = 0.83），但这是具有已知脱靶结合的区域。SUVR是适度的，CTE和非CTE病例在某些区域具有重叠的SUVR和不一致的p-tau密度。Flortaucipir-PET可用于检测高阶段CTE神经病理学，但对CTE p-tau的特异性尚不确定。在海马和丘脑中的脱靶flortaucipir结合使这些关联的解释复杂化。需要可以检测整个疾病连续体中CTE的特异性p-tau的体内生物标志物。
Flourine-18-flortaucipir tau positron emission tomography (PET) was developed for the detection for Alzheimer’s disease. Human imaging studies have begun to investigate its use in chronic traumatic encephalopathy (CTE). Flortaucipir-PET to autopsy correlation studies in CTE are needed for diagnostic validation. We examined the association between end-of-life flortaucipir PET and postmortem neuropathological measurements of CTE-related tau in six former American football players. Three former National Football League players and three former college football players who were part of the DIAGNOSE CTE Research Project died and agreed to have their brains donated. The six players had flortaucipir (tau) and florbetapir (amyloid) PET prior to death. All brains from the deceased participants were neuropathologically evaluated for the presence of CTE. On average, the participants were 59.0 (SD = 9.32) years of age at time of PET. PET scans were acquired 20.33 (SD = 13.08) months before their death. Using Spearman correlation analyses, we compared flortaucipir standard uptake value ratios (SUVRs) to digital slide-based AT8 phosphorylated tau (p-tau) density in a priori selected composite cortical, composite limbic, and thalamic regions-of-interest (ROIs). Four brain donors had autopsy-confirmed CTE, all with high stage disease (n = 3 stage III, n = 1 stage IV). Three of these four met criteria for the clinical syndrome of CTE, known as traumatic encephalopathy syndrome (TES). Two did not have CTE at autopsy and one of these met criteria for TES. Concomitant pathology was only present in one of the non-CTE cases (Lewy body) and one of the CTE cases (motor neuron disease). There was a strong association between flortaucipir SUVRs and p-tau density in the composite cortical (ρ = 0.71) and limbic (ρ = 0.77) ROIs. Although there was a strong association in the thalamic ROI (ρ = 0.83), this is a region with known off-target binding. SUVRs were modest and CTE and non-CTE cases had overlapping SUVRs and discordant p-tau density for some regions. Flortaucipir-PET could be useful for detecting high stage CTE neuropathology, but specificity to CTE p-tau is uncertain. Off-target flortaucipir binding in the hippocampus and thalamus complicates interpretation of these associations. In vivo biomarkers that can detect the specific p-tau of CTE across the disease continuum are needed.
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影响因子：
7.1
作者：
Asken BM;Rabinovici GD
通讯作者：
Rabinovici GD
影响因子：
3.2
作者：
Bieniek KF;Cairns NJ;Crary JF;Dickson DW;Folkerth RD;Keene CD;Litvan I;Perl DP;Stein TD;Vonsattel JP;Stewart W;Dams-O'Connor K;Gordon WA;Tripodis Y;Alvarez VE;Mez J;Alosco ML;McKee AC;TBI/CTE Research Group
通讯作者：
TBI/CTE Research Group
DOI：
10.1186/s13195-021-00872-x
发表时间：
2021-08-12
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Alosco ML;Mariani ML;Adler CH;Balcer LJ;Bernick C;Au R;Banks SJ;Barr WB;Bouix S;Cantu RC;Coleman MJ;Dodick DW;Farrer LA;Geda YE;Katz DI;Koerte IK;Kowall NW;Lin AP;Marcus DS;Marek KL;McClean MD;McKee AC;Mez J;Palmisano JN;Peskind ER;Tripodis Y;Turner RW 2nd;Wethe JV;Cummings JL;Reiman EM;Shenton ME;Stern RA;DIAGNOSE CTE Research Project Investigators
通讯作者：
DIAGNOSE CTE Research Project Investigators
DOI：
10.3233/jad-170840
发表时间：
2018
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Lee CM;Jacobs HIL;Marquié M;Becker JA;Andrea NV;Jin DS;Schultz AP;Frosch MP;Gómez-Isla T;Sperling RA;Johnson KA
通讯作者：
Johnson KA
影响因子：
4
作者：
Chen, Stephen T.;Siddarth, Prabha;Small, Gary W.
通讯作者：
Small, Gary W.