Hypometabolic subtypes of AD are linked to comorbid hippocampal sclerosis and Lewy body pathology.

IF 7.6 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's Research & Therapy Pub Date : 2025-07-25 DOI:10.1186/s13195-025-01796-6

Fedor Levin, Martin Dyrba, Stefan J Teipel, Michel J Grothe

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Abstract

Background: Neuroimaging studies have identified distinct 'typical/neocortical' and 'limbic-predominant' hypometabolic subtypes of AD with different clinical and biomarker characteristics. We investigated associations of these subtypes with postmortem neuropathological measures in an observational study.

Methods: Antemortem FDG-PET scans of 74 participants from the ADNI autopsy cohort were classified into previously described typical/neocortical and limbic-predominant subtype patterns. We used Bayesian regression and ANCOVA to test associations between the subtypes and neuropathological features.

Results: Results were inconclusive for Thal phases, Braak stages, CERAD neuritic plaque scores, hippocampal tangle density, and TDP-43 pathology (BF₁₀ between 0.447 and 1.146). However, the limbic-predominant subtype was associated with hippocampal sclerosis (BF₁₀ = 3.842, moderate level of evidence), whereas the typical/neocortical subtype was associated with Lewy body pathology (BF₁₀ = 10.093, strong level of evidence).

Conclusions: These findings highlight the influence of AD and non-AD-specific pathologies on neurodegeneration patterns and may provide directions for research into hypometabolic pattern analysis as an indirect marker of comorbid pathology.

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阿尔茨海默病的低代谢亚型与共病海马硬化和路易体病理有关。

背景：神经影像学研究已经确定了阿尔茨海默病不同的“典型/新皮层”和“边缘为主”低代谢亚型，具有不同的临床和生物标志物特征。我们在一项观察性研究中调查了这些亚型与死后神经病理学指标的关系。方法：74名ADNI尸检队列参与者的死前FDG-PET扫描被划分为先前描述的典型/新皮层和边缘主导亚型模式。我们使用贝叶斯回归和ANCOVA来检验亚型与神经病理特征之间的关系。结果：在Thal期、Braak期、CERAD神经斑块评分、海马缠结密度、TDP-43病理（BF10在0.447 ~ 1.146之间）方面结果尚无定论。然而，边缘显性亚型与海马硬化相关（BF10 = 3.842，中等证据水平），而典型/新皮质亚型与路易体病理相关（BF10 = 10.093，强证据水平）。结论：这些发现突出了阿尔茨海默病和非阿尔茨海默病特异性病理对神经变性模式的影响，并可能为作为共病病理间接标志物的低代谢模式分析的研究提供方向。

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

Alzheimer's Research & Therapy 医学-神经病学

CiteScore

13.10

自引率

3.30%

发文量

172

审稿时长

>12 weeks

期刊介绍： Alzheimer's Research & Therapy is an international peer-reviewed journal that focuses on translational research into Alzheimer's disease and other neurodegenerative diseases. It publishes open-access basic research, clinical trials, drug discovery and development studies, and epidemiologic studies. The journal also includes reviews, viewpoints, commentaries, debates, and reports. All articles published in Alzheimer's Research & Therapy are included in several reputable databases such as CAS, Current contents, DOAJ, Embase, Journal Citation Reports/Science Edition, MEDLINE, PubMed, PubMed Central, Science Citation Index Expanded (Web of Science) and Scopus.