时间标签：数据日期 2026-11-05 · 生成时间 2026-11-05 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/11/02 – 2026/11/06 ｜ 情报发生日期 2026-11-05
研究问题
Finally, we discuss testable hypotheses and research priorities for determining whether systemic homeostatic resilience can be operationalized, quantified and potentially modulated therapeutically in AD.2Building the Gut-Brain Homeostatic ContinuumThe GBHC is organized around four complementary functional pillars that contribute to organismal homeostasis (Figure 2): (i) the gut ecosystem; (ii) biological barriers; (iii) inter-organ communication networks; and (iv) physiological protein trafficking and clearance.；Whether these properties can be exploited to quantify changes in systemic physiological resilience remains an important question for future research.Collectively, bEVs and hEVs constitute a complementary layer of inter-organ communication that interacts with neural, immune, endocrine and metabolic pathways.；The key question is whether coordinated protein trafficking, processing and clearance across the CNS, circulation, peripheral organs and GIT contribute to systemic proteostasis.Once present in the systemic circulation, circulating Aβ can be taken up by peripheral organs, including the liver and kidneys, which contribute to its metabolism and elimination (Ghiso et al., 2004; Tamaki et al., 2006).
方法
Advances in biomarkers, including cerebrospinal fluid (CSF) and plasma assays, molecular imaging, and more recently, disease-modifying therapies targeting amyloid pathology (Scheltens et al., 2021; Rafii and Aisen, 2025; Kobayashi et al., 2026), have further established that these pathological changes can develop many years before the emergence of overt cognitive symptoms (Sperling et al., 2011).；Although aging remains the strongest risk factor for sporadic AD and dementia, dementia is not an inevitable consequence of advanced age (Qiu and Fratiglioni, 2018).；The figure illustrates conceptual convergence rather than a succession of mutually exclusive models or a linear causal sequence of AD pathogenesis.Infographic summarizing the evolution of major conceptual frameworks in Alzheimer’s disease from 1984 to 2026, including amyloid, tau, neuroimmune, vascular, metabolic, microbiota-gut-brain, systems-biology and resilience-oriented models.
核心结论
These observations suggest that cerebral pathology alone may not be sufficient to fully explain individual differences in disease susceptibility, progression and clinical expression.This discrepancy raises a fundamental question: What enables some individuals to maintain physiological and cognitive function despite prolonged exposure to biological stressors, whereas others progressively lose this capacity?；Increasing evidence indicates that aging, genetic susceptibility, vascular and metabolic alterations, immune dysregulation, environmental exposures and lifestyle factors can influence both the accumulation of AD-related pathology and its clinical expression.；The GBHC is organized around four interconnected functional pillars that collectively preserve systemic and cerebral homeostasis.
局限
However, communication is not synonymous with homeostasis.；Early-onset AD (EOAD), however, is biologically heterogeneous and should not be considered a single distinct entity.；However, the relevance and relative contribution of these mechanisms to human neuroimmune homeostasis remain to be established (Fock and Parnova, 2023).
对本项目的价值
中高价值：属「营养感知—自噬—蛋白稳态轴」方向；mTOR / 自噬 / 蛋白质稳态栏目可用作本项目文献库与综述素材。 ｜ 价值分 3.4/5（★★★☆☆）
全文来源
PubMed PMC JATS（正文 122,743 字符，题名指纹 1.0，已过 PubMed PMCID 官方关联 + 题名指纹 + 正文长度归属校验）
原文题录
- 中文题名：阿尔茨海默病中的肠-脑稳态连续体：生理韧性与疾病进展的系统框架
- 英文标题：The Gut-Brain Homeostatic Continuum in Alzheimer's disease: a systems framework for physiological resilience and disease progression.
- 期刊与标识：Frontiers in neuroscience · PMID 42974103 · DOI 10.3389/fnins.2026.1963040 · PMC PMC13725227