NDLI: Prion-like propagation of β-amyloid aggregates in the absence of APP overexpression

Content Provider	Springer Nature : BioMed Central
Author	Ruiz-Riquelme, Alejandro Lau, Heather H. C. Stuart, Erica Goczi, Adrienn N. Wang, Zhilan Schmitt-Ulms, Gerold Watts, Joel C.
Abstract	The amyloid cascade hypothesis posits that the initiating event in Alzheimer’s disease (AD) is the aggregation and deposition of the β-amyloid (Aβ) peptide, which is a proteolytic cleavage product of the amyloid precursor protein (APP). Mounting evidence suggests that the formation and spread of prion-like Aβ aggregates during AD may contribute to disease progression. Inoculation of transgenic mice that overexpress APP with pre-formed Aβ aggregates results in the prion-like induction of cerebral Aβ deposition. To determine whether Aβ deposition can also be induced when physiological APP levels are present in the brain, we inoculated AppNL-F mice, a knock-in model of AD that avoids potential artifacts associated with APP overexpression, with Aβ aggregates derived from the brains of AD patients or transgenic mice. In all cases, induced Aβ deposition was apparent in the corpus callosum, olfactory bulb, and meningeal blood vessels of inoculated mice at 130–150 days post-inoculation, whereas uninoculated and buffer-inoculated animals exhibited minimal or no Aβ deposits at these ages. Interestingly, despite being predominantly composed of protease-resistant Aβ42 aggregates, the induced parenchymal Aβ deposits were largely diffuse and were unreactive to an amyloid-binding dye. These results demonstrate that APP overexpression is not a prerequisite for the prion-like induction of cerebral Aβ deposition. Accordingly, spreading of Aβ deposition may contribute to disease progression in AD patients.
Related Links	https://actaneurocomms.biomedcentral.com/counter/pdf/10.1186/s40478-018-0529-x.pdf
Ending Page	16
Page Count	16
Starting Page	1
File Format	HTM / HTML
ISSN	20515960
DOI	10.1186/s40478-018-0529-x
Journal	Acta Neuropathologica Communications
Issue Number	1
Volume Number	6
Language	English
Publisher	BioMed Central
Publisher Date	2018-04-03
Access Restriction	Open
Subject Keyword	Neurosciences Pathology Neurology Aβ Amyloid Prion-like transmission Propagation Knock-in mice Cerebral amyloid angiopathy Amyloid precursor protein
Content Type	Text
Resource Type	Article
Subject	Pathology and Forensic Medicine Neurology (clinical) Cellular and Molecular Neuroscience
Journal Impact Factor	6.2/2023
5-Year Journal Impact Factor	6.8/2023

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