Yu Y, Jans DC, Winblad B, Tjernberg LO, Schedin-Weiss S.
Neuronal Aβ42 is enriched in small vesicles at the presynaptic side of synapses.
Life Sci Alliance. 2018 Jun;1(3):e201800028. Epub 2018 Jun 14
PubMed.
This is an interesting study using incredible resolution to assess localization of Aβ. It supports data from our group and others that a lot of Aβ is made presynaptically. Our in vivo data suggest that 70 percent of Aβ (40 and 42) found in the interstitial fluid is made via presynaptic mechanisms.
The imaging methods used here are very good at demonstrating where Aβ42 is located, but I think it is tough to make conclusions on the negative data regarding location. That some vesicles lack synaptophysin does not necessarily mean it isn’t present; that there could be two types of Aβ-containing vesicles is intriguing, but I believe still not conclusive.
Similarly, there are other conclusive studies that demonstrate that some Aβ is made postsynaptically. For instance, Paul Worley has a nice paper looking at the role of arc postsynaptically in Aβ generation (Wu et al., 2011).
My interpretation here is that Aβ42 is enriched presynaptically in these vesicles, but we cannot rule out it is present in other locations that may be below the level of detection.
References:
Wu J, Petralia RS, Kurushima H, Patel H, Jung MY, Volk L, Chowdhury S, Shepherd JD, Dehoff M, Li Y, Kuhl D, Huganir RL, Price DL, Scannevin R, Troncoso JC, Wong PC, Worley PF.
Arc/Arg3.1 regulates an endosomal pathway essential for activity-dependent β-amyloid generation.
Cell. 2011 Oct 28;147(3):615-28.
PubMed.
Comments
Washington University
This is an interesting study using incredible resolution to assess localization of Aβ. It supports data from our group and others that a lot of Aβ is made presynaptically. Our in vivo data suggest that 70 percent of Aβ (40 and 42) found in the interstitial fluid is made via presynaptic mechanisms.
The imaging methods used here are very good at demonstrating where Aβ42 is located, but I think it is tough to make conclusions on the negative data regarding location. That some vesicles lack synaptophysin does not necessarily mean it isn’t present; that there could be two types of Aβ-containing vesicles is intriguing, but I believe still not conclusive.
Similarly, there are other conclusive studies that demonstrate that some Aβ is made postsynaptically. For instance, Paul Worley has a nice paper looking at the role of arc postsynaptically in Aβ generation (Wu et al., 2011).
My interpretation here is that Aβ42 is enriched presynaptically in these vesicles, but we cannot rule out it is present in other locations that may be below the level of detection.
References:
Wu J, Petralia RS, Kurushima H, Patel H, Jung MY, Volk L, Chowdhury S, Shepherd JD, Dehoff M, Li Y, Kuhl D, Huganir RL, Price DL, Scannevin R, Troncoso JC, Wong PC, Worley PF. Arc/Arg3.1 regulates an endosomal pathway essential for activity-dependent β-amyloid generation. Cell. 2011 Oct 28;147(3):615-28. PubMed.
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