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Scientists still debate how much different types of plaques harm the brain, with some recent evidence suggesting that microglia pack Aβ into deposits to corral the peptide and mitigate the damage (Dec 2009 news; May 2016 news; Apr 2021 news)
How exactly do amyloid plaques affect surrounding brain tissue, and does this change over time? Scientists led by Jörg Hanrieder at the University of Gothenburg, Sweden, tackled this question by using isotopically labeled Aβ to timestamp plaques as they formed in mice. As described in an October 11 preprint on bioRxiv, the authors correlated the age of each plaque with its structural characteristics, and examined the effect it had on nearby gene expression using spatial transcriptomics. They found that as plaques matured, they became more compact and fibrillar, and more synaptotoxic.
Sean Bendall at Stanford University, California, said these are the first data to confirm the idea that older, more fibrillar plaques cause more havoc. “This is an important contribution that directly links the age of aggregated protein with overall disease pathology—reinforcing that these aggregates are relevant targets for intervention,”.
- In mice, the oldest amyloid plaques wreaked the greatest synaptic damage.
- The older the plaques, the more immune response they provoked.
- These more fibrillar plaques are the most synaptotoxic.
Wood JI, Dulewicz M, Ge J, Stringer K, Szadziewska A, Desai S, Koutarapu S, Hajar HB, Blennow K, Zetterberg H, Cummings DM, Savas JN, Edwards FA, Hanrieder J. Isotope Encoded Chemical Imaging Identifies Amyloid Plaque Age Dependent Structural Maturation, Synaptic Loss, and Increased Toxicity. 2024 Oct 11 10.1101/2024.10.08.617019 (version 1) bioRxiv.
Alzheimer's Association
Dementia Researcher