- Brain Pathology（Keszycki、Geula、Gefen 等，西北大学 Mesulam 中心）：47 例尸检证实的 FTLD-tau，用数字病理定量杏仁核的磷酸化 tau 与 HLA-DR（MHC-II）免疫反应性。
- 主要发现：tau 负荷相当时，行为变异型额颞叶痴呆（bvFTD）的杏仁核神经炎症重于原发性进行性失语（PPA）；3R tau（Pick 病）病例的磷酸化 tau 和 MHC-II 阳性小胶质细胞均高于 4R（CBD、PSP）。
- Pick 病亚组（19 例：bvFTD 10、PPA 9）：PPA 患者随病程逐渐出现 bvFTD 样神经精神症状；HLA-DR 与 Pick 小体负荷正相关；含 tau 的 Pick 细胞明显大于未受累神经元，提示 tau 蓄积早于明显的神经元变性。
- 读片提示：评估 FTLD 杏仁核时，小胶质细胞活化（HLA-DR）可能比 tau 负荷更贴近行为症状表型。本站仅获摘要。
收录范围：PubMed 摘要中英对照。原文为 Wiley 开放获取（CC BY），但出版社页面被 Cloudflare 拦截，本站未获全文与图表。
摘要
伴 tau 蛋白病的额颞叶变性（FTLD-tau）通常表现为行为变异型额颞叶痴呆（bvFTD）或原发性进行性失语（PPA）。FTLD-tau 的 tau 病理以三重复（3R）tau 为主（如 Pick 病，PiD），或为皮质基底节变性（CBD）和进行性核上性麻痹（PSP）的四重复（4R）tau。FTLD-tau 优先累及额叶和前颞叶（包括杏仁核），导致严重的神经精神症状。本研究探讨由 FTLD-tau 所致的 bvFTD 与 PPA 是否表现出不同的杏仁核组织病理，以及这些模式是否反映其最初不同的临床表型，尤其是在 PiD 中。我们检查了西北大学阿尔茨海默病研究中心脑库的 47 例尸检证实的 FTLD-tau 病例，采用死后数字病理分析定量杏仁核的 tau 磷酸化和 HLA-DR 免疫反应性。在其中 19 例 PiD 亚组（10 例 bvFTD-PiD，9 例 PPA-PiD）中，我们评估了用神经精神量表问卷（NPI-Q）纵向追踪的神经精神症状，并通过无偏体视学定量神经元和 Pick 小体密度、通过数字病理分析测量神经元大小。在整个 FTLD-tau 队列中，尽管 tau 负荷相当，bvFTD 的杏仁核神经炎症程度高于 PPA。有意思的是，3R 病例的磷酸化 tau 和 MHC-II 阳性小胶质细胞水平也高于 4R 病例。在 PiD 中，神经精神症状随时间趋同，PPA 病例随疾病进展逐渐出现 bvFTD 样症状。尽管神经元大小/密度和 Pick 小体负荷相近，bvFTD-PiD 的 MHC-II 阳性小胶质细胞有多于 PPA-PiD 的趋势。HLA-DR 免疫反应性增高与 Pick 小体病理呈正相关。含 tau 病理的神经元（Pick 细胞）明显大于未受累神经元，提示早期 tau 蓄积先于明显的神经元变性。这些发现强调了神经炎症在塑造 FTLD 临床表型中可能发挥的作用，并凸显了杏仁核在复杂临床病理关系中的角色。靶向神经炎症过程可能是处理 tau 蛋白病神经精神症状的可行治疗途径。
- Brain Pathology (Keszycki, Geula, Gefen and colleagues, Northwestern Mesulam Center): digital pathology quantification of phosphorylated tau and HLA-DR (MHC-II) immunoreactivity in the amygdala of 47 autopsy-confirmed FTLD-tau cases.
- Main findings: with comparable tau burden, bvFTD showed greater amygdalar neuroinflammation than PPA; 3R tau (Pick disease) cases had more phosphorylated tau and MHC-II-positive microglia than 4R cases (CBD, PSP).
- Pick disease subset (19: 10 bvFTD, 9 PPA): PPA cases developed bvFTD-like neuropsychiatric symptoms over time; HLA-DR correlated with Pick body burden; tau-bearing Pick cells were larger than unaffected neurons, suggesting tau accumulation precedes overt neuronal degeneration.
- Practice point: in the FTLD amygdala, microglial activation (HLA-DR) may track the behavioural phenotype more closely than tau burden. Abstract only.
Scope: the PubMed abstract. The article is Wiley open access (CC BY), but the publisher page was blocked by Cloudflare for our fetcher, so the full text and figures were not obtained.
Abstract
Frontotemporal lobar degeneration with tauopathy (FTLD-tau) typically manifests as either behavioral variant frontotemporal dementia (bvFTD) or primary progressive aphasia (PPA). Tau pathology in FTLD-tau is characterized by predominantly three-repeat (3R) tau, as in Pick disease (PiD), or four-repeat (4R) tau species of corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). FTLD-tau preferentially targets frontal and anterior temporal lobes, including the amygdala, contributing to severe neuropsychiatric symptoms. This study investigated whether bvFTD and PPA due to FTLD-tau exhibit distinct amygdalar histopathology and whether these patterns reflect their initially distinct clinical phenotypes, particularly in PiD. We examined 47 autopsy-confirmed FTLD-tau cases from the Northwestern Alzheimer's Disease Research Center Brain Bank using postmortem digital pathology analysis to quantify tau phosphorylation and HLA-DR immunoreactivity in the amygdala. In a subset of 19 PiD cases (10 bvFTD-PiD, 9 PPA-PiD), we assessed neuropsychiatric symptoms, tracked longitudinally using the Neuropsychiatric Inventory-Questionnaire (NPI-Q), and quantified neuronal and Pick body densities via unbiased stereology and neuronal sizes via digital pathology analysis. Across the FTLD-tau cohort, bvFTD exhibited greater amygdalar neuroinflammation than PPA, despite comparable tau burden. Interestingly, 3R cases also demonstrated higher levels of phosphorylated tau and MHC-II-positive microglia than 4R cases. In PiD, neuropsychiatric symptoms converged over time, with PPA cases evolving to show bvFTD-like symptoms with disease progression. BvFTD-PiD showed a trend toward greater MHC-II-positive microglia than PPA-PiD, despite similar neuronal size/density and Pick body burden. Increased HLA-DR immunoreactivity correlated positively with Pick body pathology. Neurons containing tau pathology (Pick cells) were notably larger than unaffected neurons, suggesting that early tau accumulation precedes overt neuronal degeneration. These findings underscore the potential role of neuroinflammation in shaping clinical phenotypes in FTLD and highlight the role of the amygdala in complex clinicopathologic relationships. Targeting neuroinflammatory processes may represent a viable therapeutic avenue for managing neuropsychiatric symptoms in tauopathies.