Following spatial Aβ aggregation dynamics in evolving Alzheimer's disease pathology by imaging stable isotope labeling kinetics.

Michno W, Stringer KM, Enzlein T, Passarelli MK, Escrig S, Vitanova K, Wood J, Blennow K, Zetterberg H, Meibom A, Hopf C, Edwards FA, Hanrieder J

Sci Adv 7 (25) - [2021-06-00; online 2021-06-16]

β-Amyloid (Aβ) plaque formation is the major pathological hallmark of Alzheimer's disease (AD) and constitutes a potentially critical, early inducer driving AD pathogenesis as it precedes other pathological events and cognitive symptoms by decades. It is therefore critical to understand how Aβ pathology is initiated and where and when distinct Aβ species aggregate. Here, we used metabolic isotope labeling in APP knock-in mice together with mass spectrometry imaging to monitor the earliest seeds of Aβ deposition through ongoing plaque development. This allowed visualizing Aβ aggregation dynamics within single plaques across different brain regions. We show that formation of structurally distinct plaques is associated with differential Aβ peptide deposition. Specifically, Aβ1-42 is forming an initial core structure followed by radial outgrowth and late secretion and deposition of Aβ1-38. These data describe a detailed picture of the earliest events of precipitating amyloid pathology at scales not previously possible.NL-G-F

SciLifeLab Fellow

Wojciech Michno

PubMed 34134980

DOI 10.1126/sciadv.abg4855

Crossref 10.1126/sciadv.abg4855

pmc: PMC8208724
pii: 7/25/eabg4855

Publications 9.5.0