PT  - JOURNAL ARTICLE
AU  - Yang Yu
AU  - Daniel C Jans
AU  - Bengt Winblad
AU  - Lars O Tjernberg
AU  - Sophia Schedin-Weiss
TI  - Neuronal Aβ42 is enriched in small vesicles at the presynaptic side of synapses
AID  - 10.26508/lsa.201800028
DP  - 2018 Jun 01
TA  - Life Science Alliance
PG  - e201800028
VI  - 1
IP  - 3
4099  - https://www.life-science-alliance.org/content/1/3/e201800028.short
4100  - https://www.life-science-alliance.org/content/1/3/e201800028.full
SO  - Life Sci. Alliance2018 Jun 01; 1
AB  - The amyloid β-peptide (Aβ) is a physiological ubiquitously expressed peptide suggested to be involved in synaptic function, long-term potentiation, and memory function. The 42 amino acid-long variant (Aβ42) forms neurotoxic oligomers and amyloid plaques and plays a key role in the loss of synapses and other pathogenic events of Alzheimer disease. Still, the exact localization of Aβ42 in neurons and at synapses has not been reported. Here, we used super-resolution microscopy and show that Aβ42 was present in small vesicles in presynaptic compartments, but not in postsynaptic compartments, in the neurites of hippocampal neurons. Some of these vesicles appeared to lack synaptophysin, indicating that they differ from the synaptic vesicles responsible for neurotransmitter release. The Aβ42-containing vesicles existed in presynapses connected to stubby spines and mushroom spines, and were also present in immature presynapses. These vesicles were scarce in other parts of the neurites, where Aβ42 was instead present in large, around 200–600 nm, vesicular structures. Three-dimensional super-resolution microscopy confirmed that Aβ42 was present in the presynapse and absent in the postsynapse.