Neuronal A beta 42 is enriched in small vesicles at the presynaptic side of synapses

• The amyloid beta-peptide (A beta) 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 (A beta 42) 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 A beta 42 in neurons and at synapses has not been reported. Here, we used super-resolution microscopy and show that A beta 42 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 A beta 42-containing vesicles existed in presynapses connected to stubby spines and mushroom spines, and were also present in immature presynapses. These vesicleswere scarce inother parts of the neurites, where A beta 42 was instead present in large, around 200-600 nm, vesicular structures. Three-dimensional super-resolution microscopy confirmed that A beta 42 was present in the presynapse and absent in the postsynapse.

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MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

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