Is Stroke a Neurodegenerative Condition? A Critical Review of Secondary Neurodegeneration and Amyloid-beta Accumulation after Stroke

Abstract

Stroke-induced secondary neurodegeneration (SND) refers to the progressive and inexorable loss of tissues at sites connected to area damaged by the initial infarction. SND has been consistently observed to occur in humans and rodents after stroke. Intriguingly, stroke-induced SND shares a number of striking similarities to other neurodegenerative diseases such as Alzheimer’s disease, most notably with respect to the significant accumulation of the neurotoxic protein amyloid-β. Together, this observation and others (progressive neuronal loss and neuroinflammation) suggest the possibility that stroke may induce a neurodegenerative condition. Certainly, this is supported to some degree by the relatively high incidence of dementia after stroke. We begin this review by addressing the available research on human and rodent SND pathology after stroke. We next consider amyloid-β in the context of SND. We discuss what amyloid-β is, how is it made, and introduce some caveats on how amyloid-β measurements should be interpreted. In summary, we conclude that there is now robust pre-clinical evidence demonstrating the presence of amyloid disturbances at sites of SND after stroke. We find, however, that the human literature on the topic is more limited and further work is warranted. While the understanding of amyloid disturbances remains inconclusive in human studies, stroke clearly lead to the development of a neurodegenerative-like condition at the sites of SND, with prominent features such as death of neurons and gliosis.