SignificanceWhile amyloid pores were first reported nearly two decades ago, their nature and relevance to diseases remain unclear. Here, we characterize loop-like structures in protofibrillar assemblies derived from human Alzheimer’s disease brains. We find that the flexibility of such ex vivo protofibrils enables their two ends to meet to form pore-like structures. The ends of the chains can also dissociate to adopt extended conformations such that they can exist in both open and closed states. These findings suggest that the formation of amyloid loops is a generic process, governed by the fact that intermediate protofibrillar species behave as semiflexible polymers, thus adding to our overall understanding of the formation of disease-relevant protein assembly states.