The proteinopenia hypothesis: Loss of Aβ42 and the onset of Alzheimer's Disease

Alberto J Espay; Karl Herrup; Kasper P Kepp; Timothy Daly

doi:10.1016/j.arr.2023.102112

The proteinopenia hypothesis: Loss of Aβ₄₂ and the onset of Alzheimer's Disease

Ageing Res Rev. 2023 Dec:92:102112. doi: 10.1016/j.arr.2023.102112. Epub 2023 Oct 28.

Authors

Alberto J Espay¹, Karl Herrup², Kasper P Kepp³, Timothy Daly⁴

Affiliations

¹ James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, USA. Electronic address: alberto.espay@uc.edu.
² Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
³ Department of Chemistry, Section of Biophysical and Biomedicinal Chemistry, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.
⁴ Science Norms Democracy, UMR 8011 Sorbonne University, Paris, France; Bioethics Program, FLACSO Argentina, Tucumán 1966, C1050 AAN, Buenos Aires, Argentina. Electronic address: tdaly@flacso.org.ar.

PMID: 38270185
DOI: 10.1016/j.arr.2023.102112

Abstract

The dominant protein-lowering strategy in Alzheimer's Disease (AD) has failed to provide a clinically-meaningful treatment for patients. We hypothesize that the loss of functional, soluble Aβ42 during the process of aggregation into amyloid is more detrimental to the brain than the corresponding accrual of insoluble amyloid.

Keywords: Alzheimer's disease; Amyloid; Aβ42; Loss of function; Soluble protein.

Publication types

Review

MeSH terms

Alzheimer Disease*
Amyloidogenic Proteins
Brain
Humans

Substances

Amyloidogenic Proteins