Amyloid beta-protein (A beta) sequence length variants with varying aggregation propensity coexist in vivo, where coaggregation and cross-catalysis phenomena may affect the aggregation process. Until recently, naturally occurring amyloid beta-protein (A beta) variants were believed to begin at or after the canonical beta-secretase cleavage site within the amyloid beta-protein precursor. However, N-terminally extended forms of A beta (NTE-A beta) were recently discovered and may contribute to Alzheimers disease. Here, we have used thioflavin T fluorescence to study the aggregation kinetics of A beta 42 variants with N-terminal extensions of 540 residues, and transmission electron microscopy to analyze the end states. We find that all variants form amyloid fibrils of similar morphology as A beta 42, but the half-time of aggregation (t(1/2)) increases exponentially with extension length. Monte Carlo simulations of model peptides suggest that the retardation is due to an underlying general physicochemical effect involving reduced frequency of productive molecular encounters. Indeed, global kinetic analyses reveal that NTE-A beta 42s form fibrils via the same mechanism as A beta 42, but all microscopic rate constants (primary and secondary nucleation, elongation) are reduced for the N-terminally extended variants. Still, A beta 42 and NTE-A beta 42 coaggregate to form mixed fibrils and fibrils of either A beta 42 or NTE-A beta 42 catalyze aggregation of all monomers. NTE-A beta 42 monomers display reduced aggregation rate with all kinds of seeds implying that extended termini interfere with the ability of monomers to nucleate or elongate. Cross-seeding or coaggregation may therefore represent an important contribution in the in vivo formation of assemblies believed to be important in disease.