边缘为主型与年龄相关的 TDP-43 蛋白病脑病理改变（LATE-NC）的神经病理学关联在最年长和较年轻的老年人之间存在差异。
Neuropathological associations of limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) differ between the oldest-old and younger-old.
机构信息
Department of Pathology, Duke University Medical Center, 214MA Davison Bldg., 40 Duke Medicine Circle, Durham, NC, 27710, USA.
Department of Neurology, Duke University Medical Center, Durham, USA.
出版信息
Acta Neuropathol. 2022 Jul;144(1):45-57. doi: 10.1007/s00401-022-02432-5. Epub 2022 May 12.
Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) is most often seen in the oldest-old (≥ 90 years of age) but can also be present in the younger-old (< 90 years of age). In this study, we compared the neuropathological associations of LATE-NC and contribution of LATE-NC to cognitive impairment between the oldest-old and younger-old. We observed significant differences in the prevalence of LATE-NC and its association with other co-pathologies in these two age groups. LATE-NC was present in 30.9% (34/110) of the oldest-old but only 9.4% (19/203) of the younger-old. Participants of the oldest-old with LATE-NC were more likely to have hippocampal sclerosis (HS) (55.9% vs. 10.5%, p < 0.001) and moderate to severe arteriolosclerosis (82.4% vs. 50%, p = 0.007), but not intermediate to high Alzheimer's disease neuropathologic change (ADNC) (70.6% vs. 59.2%, p = 0.486) or Lewy body disease (LBD) (20.6% vs. 26.3%, p = 0.793). Participants of the younger-old with LATE-NC were more likely to have intermediate to high ADNC (94.7% vs. 55.4%, p < 0.001) and LBD (63.2% vs. 28.8%, p = 0.013) in addition to hippocampal sclerosis (42.1% vs. 6.5%, p < 0.001), and moderate to severe arteriolosclerosis (42.1% vs. 15.2%, p = 0.020). Of note, participants with LATE-NC and no to low ADNC were very rare in the younger-old (< 1%) but relatively common in the oldest-old (9.1%). Logistic regression modeling showed that in the oldest-old, both intermediate to high ADNC and LATE-NC were independently associated with higher odds of having dementia (OR: 5.09, 95% CI [1.99, 13.06], p < 0.001 for ADNC; OR: 3.28, 95% CI [1.25, 8.57], p = 0.015 for LATE-NC). In the younger-old, by contrast, intermediate to high ADNC and LBD were independently associated with higher odds of having dementia (OR: 4.43, 95% CI [2.27, 8.63], p < 0.001 for ADNC; OR: 2.55, 95% CI [1.21, 5.35], p < 0.014 for LBD), whereas LATE-NC did not show an independent association with dementia. Overall, LATE-NC is strongly associated with arteriolosclerosis and HS in both groups; however, in the younger-old, LATE-NC is associated with other neurodegenerative pathologies, such as ADNC and LBD; whereas in the oldest-old, LATE-NC can exist independent of significant ADNC.
边缘为主型与年龄相关的 TDP-43 蛋白病脑病理改变（LATE-NC）最常发生在年龄最大的老年人（≥90 岁），但也可发生在年龄较小的老年人（<90 岁）。在这项研究中，我们比较了 LATE-NC 在最年长组和年轻组中的神经病理学关联及其对认知障碍的影响。我们观察到这两个年龄组中 LATE-NC 的患病率及其与其他共病的相关性存在显著差异。在最年长组中，LATE-NC 的患病率为 30.9%（34/110），而在年轻组中为 9.4%（19/203）。患有 LATE-NC 的最年长组参与者更有可能出现海马硬化（HS）（55.9% vs. 10.5%，p<0.001）和中度至重度小动脉硬化（82.4% vs. 50%，p=0.007），但没有中度至高度阿尔茨海默病神经病理改变（ADNC）（70.6% vs. 59.2%，p=0.486）或路易体病（LBD）（20.6% vs. 26.3%，p=0.793）。患有 LATE-NC 的年轻组参与者更有可能出现中度至高度 ADNC（94.7% vs. 55.4%，p<0.001）和 LBD（63.2% vs. 28.8%，p=0.013），此外还伴有 HS（42.1% vs. 6.5%，p<0.001）和中度至重度小动脉硬化（42.1% vs. 15.2%，p=0.020）。值得注意的是，年轻组中 LATE-NC 且 ADNC 为无至低水平的参与者非常少见（<1%），但在最年长组中相对常见（9.1%）。逻辑回归模型显示，在最年长组中，中度至高度 ADNC 和 LATE-NC 均与痴呆的发病风险增加独立相关（OR：5.09，95%CI [1.99, 13.06]，p<0.001 用于 ADNC；OR：3.28，95%CI [1.25, 8.57]，p=0.015 用于 LATE-NC）。相比之下，在年轻组中，中度至高度 ADNC 和 LBD 与痴呆的发病风险增加独立相关（OR：4.43，95%CI [2.27, 8.63]，p<0.001 用于 ADNC；OR：2.55，95%CI [1.21, 5.35]，p<0.014 用于 LBD），而 LATE-NC 与痴呆无独立相关性。总体而言，LATE-NC 与两组中的小动脉硬化和 HS 强烈相关；然而，在年轻组中，LATE-NC 与其他神经退行性病变相关，如 ADNC 和 LBD；而在最年长组中，LATE-NC 可独立于明显的 ADNC 存在。
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