Progression of Seed-Induced Aβ Deposition within the Limbic Connectome.
Progression of Seed-Induced Aβ Deposition within the Limbic Connectome.
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DOI：
10.1111/bpa.12252
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发表时间：
2015-11
期刊：
影响因子：
--
通讯作者：
Walker LC
中科院分区：
文献类型：
--
作者：
Ye L;Hamaguchi T;Fritschi SK;Eisele YS;Obermüller U;Jucker M;Walker LC
An important early event in the pathogenesis of Alzheimer’s disease (AD) is the aberrant polymerization and extracellular accumulation of amyloid-β peptide (Aβ). In young transgenic mice expressing the human Aβ-precursor protein (APP), deposits of Aβ can be induced by the inoculation of minute amounts of brain extract containing Aβ aggregates (“Aβ seeds”), indicative of a prion-like seeding phenomenon. Moreover, focal intracerebral injection of Aβ seeds can induce deposits not only in the immediate vicinity of the injection site, but, with time, also in distal regions of the brain. However, it remains uncertain whether the spatial progression of Aβ deposits occurs via nonsystematic diffusion from the injection site to proximal regions or via directed transit along neuroanatomical pathways. To address this question, we analyzed the spatiotemporal emergence of Aβ deposits in two different APP-transgenic mouse models that had been previously inoculated with Aβ seeds into the hippocampal formation. The results revealed a specific, neuroanatomically constrained pattern of induced Aβ deposits in structures corresponding to the limbic connectome, supporting the hypothesis that neuronal pathways act as conduits for the movement of proteopathic agents among brain regions, thereby facilitating the progression of disease.
