Pure limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (pure LATE-NC) is a term used to describe brains with LATE-NC but lacking intermediate or severe levels of Alzheimer’s disease neuropathologic changes (ADNC). Focusing on pure LATE-NC, we analyzed data from the National Alzheimer’s Coordinating Center (NACC) Neuropathology Data Set, comprising clinical and pathological information aggregated from 32 NIH-funded Alzheimer’s Disease Research Centers (ADRCs). After excluding subjects dying with unusual conditions, n = 1,926 autopsied subjects were included in the analyses. For > 90% of these participants, apolipoprotein E (APOE) allele status was known; 46.5% had at least one APOE 4 allele. In most human populations, only 15–25% of people are APOE ε4 carriers. ADRCs with higher documented AD risk allele (APOE or BIN1) rates had fewer participants lacking ADNC, and correspondingly low rates of pure LATE-NC. Among APOE ε4 non-carries, 5.3% had pure LATE-NC, 37.0% had pure ADNC, and 3.6% had pure neocortical Lewy body pathology. In terms of clinical impact, participants with pure LATE-NC tended to die after having received a diagnosis of dementia: 56% died with dementia among APOE ε4 non-carrier participants, comparable to 61% with pure ADNC. LATE-NC was associated with increased Clinical Dementia Rating Sum of Boxes (CDR-SOB) scores, i.e. worsened global cognitive impairments, in participants with no/low ADNC and no neocortical Lewy body pathology (p = 0.0023). Among pure LATE-NC cases, there was a trend for higher LATE-NC stages to be associated with worse CDR-SOB scores (p = 0.026 for linear trend of LATE-NC stages). Pure LATE-NC was not associated with clinical features of disinhibition or primary progressive aphasia. In summary, LATE-NC with no or low levels of ADNC was less frequent than pure ADNC but was not rare, particularly among individuals who lacked the APOE 4 allele, and in study cohorts with APOE 4 frequencies similar to those in most human populations.

纯边缘系统为主的年龄相关性 TDP-43 脑病神经病理学改变 （纯 LATE-NC） 是一个术语，用于描述患有 LATE-NC 但缺乏中度或重度阿尔茨海默病神经病理学变化 （ADNC） 的大脑。我们专注于纯 LATE-NC，分析了来自国家阿尔茨海默病协调中心 （NACC） 神经病理学数据集的数据，其中包括来自 32 个 NIH 资助的阿尔茨海默病研究中心 （ADRC） 汇总的临床和病理信息。在排除因异常情况死亡的受试者后，n = 1,926 名尸检受试者被纳入分析。对于 >，90% 的参与者已知载脂蛋白 E （APOE） 等位基因状态;46.5% 的患者至少有一个 APOE 4 等位基因。在大多数人类群体中，只有 15-25% 的人是 APOE ε4 携带者。记录在 AD 风险等位基因 （APOE 或 BIN1） 率较高的 ADRC 缺乏 ADNC 的参与者较少，因此纯 LATE-NC 的发生率较低。在 APOE ε4 非携带者中，5.3% 为纯 LATE-NC，37.0% 为纯 ADNC，3.6% 为纯新皮层路易体病变。就临床影响而言，纯 LATE-NC 参与者在被诊断为痴呆后往往死亡：在 APOE ε4 非携带者参与者中，56% 死于痴呆，与纯 ADNC 的 61% 相当。LATE-NC 与临床痴呆评定量和框 （CDR-SOB） 评分增加相关，即 在无/低 ADNC 且无新皮质路易体病理的参与者中，整体认知障碍恶化 （p = 0.0023）。在纯 LATE-NC 病例中，较高的 LATE-NC 分期与较差的 CDR-SOB 评分相关（LATE-NC 分期的线性趋势 p = 0.026）。 纯 LATE-NC 与去抑制或原发性进行性失语症的临床特征无关。总之，没有或低水平 ADNC 的 LATE-NC 比纯 ADNC 少，但并不罕见，尤其是在缺乏 APOE 4 等位基因的个体中，以及 APOE 4 频率与大多数人群相似的研究队列中。