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From Soluble Aβ to Progressive Aβ Aggregation: Could Prion-Like Templated Misfolding Play a Role?


  • Yvonne S. Eisele

    Corresponding author
    1. Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
    • DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany
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Corresponding author:

Yvonne S. Eisele, PhD, German Center for Neurodegenerative Diseases (DZNE), c/o Hertie-Institute for Clinical Brain Research, Otfried-Müller-Straße 27, D-72076 Tübingen, Germany (E-mail:


Accumulation, aggregation and deposition of Aβ peptides are pathological hallmarks in the brains of individuals affected by Alzheimer's disease (AD) or by cerebral β-amyloid angiopathy (Aβ-CAA). While Aβ is a peptide of yet largely unknown function, it is constantly produced in the human brain where it normally remains in a soluble state. However, Aβ peptides are aggregation prone by their intrinsic ability to adopt alternative conformations rich in β-sheet structure that aggregate into oligomeric as well as fibrillar formations. This transition from soluble to aggregated state has been hypothesized to initiate the pathological cascade and is therefore subject to intensive research. Mounting evidence suggests prion-like templated misfolding as the biochemical phenomenon responsible for promoting progressive Aβ aggregation. Here, we review studies in vitro and in vivo that suggest that cerebral Aβ aggregation may indeed progress via prion-like templated misfolding. The implications of these findings are discussed with respect to understanding initiation and progression of the disease and to developing therapeutics.