A Unifying Mechanism for Synaptic Amyloid β Toxicity β Adrenergic Potentiation of the Ca <sup>2+</sup> Channel CaV1.2 by Amyloid β
permeable (CP) AMPARs in hippocampal cultures and impairs LTP in hippocampal slices within minutes. The long-term consequence is a loss of postsynaptic structure of glutamatergic synapses and neurotoxicity. Disrupting this signaling cascade with highly specific tools prevented all of these effects, unifying a number of currently divergent findings on Aβ synaptotoxicity including dysregulation of AMPARs and synaptic plasticity. TEASER: <100 nM), synaptic dysfunction and ultimately neuronal death. This work identifies an essential mechanism in amyloid β neurotoxicity and explains many of the observed postsynaptic alterations. Highlights: .
Authors
- James D. Scripter (ORCID: https://orcid.org/0000-0002-4448-759X)
- Johannes Hell (ORCID: https://orcid.org/0000-0001-7960-7531)
- Manuel F. Navedo (ORCID: https://orcid.org/0000-0001-6864-6594)
- Madeline Nieves‐Cintrón (ORCID: https://orcid.org/0000-0003-1935-8400)
- Mary C. Horne (ORCID: https://orcid.org/0000-0002-2799-3212)
- Yang K. Xiang (ORCID: https://orcid.org/0000-0003-1786-9143)
- Zoila M. Estrada‐Tobar (ORCID: https://orcid.org/0000-0002-4212-5325)
- Peter Bartels (ORCID: https://orcid.org/0000-0001-5852-1835)
- Chao-Yin Chen
- Andranik Avedisyan
- Ariel Jacobi
- Ruben Berumen
- Sarah Rouge
- Zhuoer Zeng
- Jennifer Price
- Shen-Yang Ho
Institutions
- West Virginia University (US)
- Blanchette Rockefeller Neurosciences Institute (US)
- VA Northern California Health Care System (US)
- University of California, Davis (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-04-29
- DOI
- https://doi.org/10.64898/2026.04.25.720803
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Alzheimer's Association
- Office of Research and Development
- National Institute on Aging
- National Institute of General Medical Sciences
- National Institute of Neurological Disorders and Stroke
- Common Fund