Isolated medial temporal lobe amnesia (MTLA): Predictor of cerebral amyloidosis or marker of phenotype-specific vulnerability?

IF 2.3 4区医学 Q2 CLINICAL NEUROLOGY

Revue neurologique Pub Date : 2026-04-01 Epub Date: 2026-03-02 DOI:10.1016/j.neurol.2026.02.149

G. Pin , T. Horowitz , E. Guedj , O. Felician , M. Ceccaldi , L. Koric

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引用次数: 0

Abstract

Background

Medial temporal lobe amnestic syndrome (MTLA) is classically considered a hallmark of Alzheimer's disease (AD). However, emerging evidence suggests etiological heterogeneity, challenging the assumption that MTLA universally reflects AD pathology.

Objective

To determine the prevalence of amyloid pathology in isolated MTLA, identify phenotypic and genetic risk factors, and characterize associated network vulnerabilities in amnestic mild cognitive impairment (aMCI).

Method

This retrospective observational study analyzed 55 patients with isolated MTLA at the aMCI stage. Participants underwent neuropsychological testing, cerebrospinal fluid (CSF) biomarker analysis, amyloid PET, and 18FDG-PET. Patients were stratified by amyloid status (positive/negative) and compared for APOE genotype, clinical features, and metabolic patterns. Statistical analyses included the Kruskal-Wallis test for non-parametric group comparisons and chi-square tests for categorical genetic associations.

Results

Amyloid pathology was observed in only 67% (37/55) of MTLA patients, dissociating the syndrome from AD in one-third of cases. Amyloid-positive patients demonstrated a significantly higher APOE ɛ4 carrier rate compared to amyloid-negative peers (χ² = 7.02, df = 2, P = 0.030), while 18FDG-PET revealed inferotemporal hypometabolism in amyloid-positive cases, marking early decontextualized memory impairment.

Conclusion

MTLA syndrome is not homogeneous on the biological level and amyloid pathology and APOE ɛ4 genotype stratify patients into distinct subgroups. Amyloid-positive cases demonstrate inferotemporal hypometabolism, suggesting AD-related network vulnerability. By contrast, amyloid-negative MTLA group shows no systemic brain network vulnerabilities, likely due to its heterogeneous etiological origins. These findings advocate for a precision medicine framework integrating biomarkers to guide therapeutic strategies, moving beyond syndromic diagnoses to target underlying mechanisms.

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孤立性内侧颞叶遗忘症（MTLA）：脑淀粉样变性的预测因子还是表型特异性易感性的标志？

背景：内侧颞叶遗忘综合征（MTLA）通常被认为是阿尔茨海默病（AD）的标志。然而，新出现的证据表明病因异质性，挑战了MTLA普遍反映AD病理的假设。目的：确定分离MTLA中淀粉样蛋白病理的患病率，确定表型和遗传危险因素，并表征遗忘性轻度认知障碍（aMCI）的相关网络脆弱性。方法：回顾性观察分析55例aMCI期孤立性MTLA患者。参与者接受了神经心理测试、脑脊液（CSF）生物标志物分析、淀粉样蛋白PET和18FDG-PET。根据淀粉样蛋白状态（阳性/阴性）对患者进行分层，并比较APOE基因型、临床特征和代谢模式。统计分析包括用于非参数组比较的Kruskal-Wallis检验和用于分类遗传关联的卡方检验。结果：只有67%（37/55）的MTLA患者出现淀粉样蛋白病理，三分之一的患者将该综合征与AD分离。淀粉样蛋白阳性患者的APOE / 4携带率明显高于淀粉样蛋白阴性患者（χ2=7.02, df=2， P=0.030），而淀粉样蛋白阳性患者的18FDG-PET显示颞下代谢低下，提示早期去情境化记忆障碍。结论：MTLA综合征在生物学水平上具有非同质性，淀粉样蛋白病理和APOE / 4基因型将患者划分为不同的亚组。淀粉样蛋白阳性的病例表现为颞下代谢低下，提示ad相关的网络脆弱性。相比之下，淀粉样蛋白阴性的MTLA组没有表现出系统性的脑网络脆弱性，这可能是由于其异质性的病因。这些发现提倡一个整合生物标志物的精准医学框架来指导治疗策略，超越综合征诊断，瞄准潜在机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Revue neurologique 医学-临床神经学

CiteScore

4.80

自引率

0.00%

发文量

598

审稿时长

55 days

期刊介绍： The first issue of the Revue Neurologique, featuring an original article by Jean-Martin Charcot, was published on February 28th, 1893. Six years later, the French Society of Neurology (SFN) adopted this journal as its official publication in the year of its foundation, 1899. The Revue Neurologique was published throughout the 20th century without interruption and is indexed in all international databases (including Current Contents, Pubmed, Scopus). Ten annual issues provide original peer-reviewed clinical and research articles, and review articles giving up-to-date insights in all areas of neurology. The Revue Neurologique also publishes guidelines and recommendations. The Revue Neurologique publishes original articles, brief reports, general reviews, editorials, and letters to the editor as well as correspondence concerning articles previously published in the journal in the correspondence column.