Abstract: The amyloid—what peptide can resist its entropic bliss? Without kinetic barricades and chaperones, most peptides would simply tumble down that precipice. The amyloid-β (Aβ) peptides are understood to underlie the hallmark pathology of Alzheimer’s disease (AD) and are considered one of the causative factors for neurodegeneration and cognitive impairment. AD affects critical connected structures within the brain that are responsible for memory, language, and social behavior. Various isoforms of Aβ peptides are produced by proteolytic cleavage of the transmembrane amyloid precursor protein (APP) by secretases, which dictates the amyloidogenic fate of the released product. Those released from α-secretase cleavage appear to be non-amyloidogenic, while β-secretase cleavage that releases fragments with intact N-termini is amyloidogenic. Further diversification occurs also through a slew of post-translational modifications, such as methionine25 oxidation and aspartate racemization, producing fragments with varying amyloidogenic tendencies. Amongst all of these isoforms, peptides Aβ1–42 and Aβ1–40 show higher propensity for aggregation, ultimately forming insoluble amyloid plaques (also termed senile plaques) present in the diseased brain (Hampel et al., 2021). This global minimum energy peptide assembly is stabilized by backbone-to-backbone in-register hydrogen bonding of peptides in the β-strand conformation. The tertiary structure of amyloid fibrils is biophysically described as β-strands perpendicular to the fibrillar axis and exhibiting the characteristic cross-β X-ray diffraction pattern (Nirmalraj et al., 2020). Quaternary structures include soluble oligomers, higher-order structures that form colloids, and yet higher-order insoluble plaque (Figure 1). Each order of amyloid aggregation is bound to exhibit its own pathological (or as more recently emergent, physiological) relevance. Factors influencing the propensity of amyloid conformation include the identity of residues, local environment, concentration, and local primary structure. The residues Arg and particularly Lys have a low β-strand propensity. Their covalent modification at the side-chain amino or guanidyl functions increases hydrophobicity—one of the promoters of the β-strand conformation.