Ludwig-Maximilians-Universität, Chair of Metabolic Biochemistry
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If amyloid drives Alzheimer disease, why have anti-amyloid therapies not yet slowed cognitive decline?

PLoS Biol. 2022 Jul 21;20(7):e3001694.

Authors/Editors: Haass C
Selkoe D
Publication Date: 2022
Type of Publication: Review

Abstract
Strong genetic evidence supports an imbalance between production and clearance of amyloid β-protein in people with Alzheimer disease. Microglia that are potentially involved in alternative mechanisms are actually integral to the amyloid cascade. Fluid biomarkers and brain imaging place accumulation of amyloid-b-protein at the beginning of molecular and clinical changes in the disease. So why have clinical trials of anti-amyloid therapies not provided clear-cut benefits to Alzheimer patients? Can anti-amyloid therapies robustly decrease amyloid b-protein in the human brain, and if so, could this lowering be too little, too late? These central questions in research on Alzheimer disease are being urgently addressed.

Figure_Amyloid-Cascade-400

Haass C, Selkoe D, 2022, PLOS Biology, CC-BY 4.0
(https://creativecommons.org/licenses/by/4.0/)

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