Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder, characterized by the accumulation of amyloid-β plaques and neurofibrillary tangles composed of hyperphosphorylated Tau. Among Tau species, the smaller, soluble oligomers are now recognized as the most neurotoxic, with the capacity to propagate in a prion-like manner across cells and brain regions. Beyond homotypic aggregation, Tau interacts with other proteins to form aggregates—referred to as hetero-amyloids—which are increasingly implicated in disease pathogenesis due to their enhanced toxicity and complex structural diversity. This study explores the formation of hetero-amyloids between Tau and the RNA-binding protein Musashi1 (MSI1),a regulator of mRNA translation and a protein associated with multiple neurodegenerative conditions. MSI1 has been observed, by our group, to aggregate and mis-localize in AD, exhibiting functional impairment in the presence of pathological Tau species. Here, the presence of MSI1:Tau hetero-amyloids is examined in human brain tissue, while recombinant approaches are used to reconstitute and biochemically characterize these aggregates as distinct molecular species. The detection of MSI1:Tau hetero-amyloids in Alzheimer’s disease brain tissue introduces a novel and promising area for therapeutic and diagnostic development. Given the reported enhanced toxicity of hetero-amyloids in neurodegenerative disease, further investigation into their structure and function may uncover critical mechanisms driving disease progression.