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Here, we employ atomic force microscopy coupled with infrared spectroscopy (AFM\u2010IR) to resolve morphological and structural heterogeneity of A\u03b240 at the single\u2010fibril level across aggregation stages. Early\u2010stage fibrils exhibit two distinct morphological polymorphs characterized by predominantly disordered structures with coexisting antiparallel \u03b2\u2010sheet motifs. Upon maturation, fibrils converge toward a single dominant polymorph and transition to parallel \u03b2\u2010sheet conformations, yielding morphologically homogeneous yet structurally heterogeneous populations. Critically, seeding experiments with isotopically labeled A\u03b240 demonstrate that the disordered polymorphs do not propagate efficiently, explaining their longstanding absence in structural studies of both in vitro and brain\u2010derived aggregates. These findings establish the transient nature of early\u2010stage antiparallel intermediates and provide mechanistic insights into fibril maturation pathways with implications for understanding amyloid polymorphism and therapeutic targeting strategies.<\/jats:p>","DOI":"10.1002\/cphc.202500818","type":"journal-article","created":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T01:34:27Z","timestamp":1776476067000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["From Disordered to Ordered: Nanoscale Spectroscopy Reveals Structural Evolution of Amyloid Beta 40 Fibrils"],"prefix":"10.1002","volume":"27","author":[{"given":"Divya","family":"Baghel","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry The University of Alabama  Tuscaloosa Alabama 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