Synergistic Interactions between Repeats in Tau Protein and Aβ Amyloids May Be Responsible for Accelerated Aggregation via

bS Supporting Information In the Alzheimer brain, the two hallmark pathological lesions,first described by Dr. Alzheimer in 1906, are senile plaques1 and neurofibrillary tangles (NFTs).2 In Alzheimer’s disease (AD), senile plaques and NFTs simultaneously aggregate. These two aggregation processes appear to occur independently be-cause the senile plaques are extracellular deposits which develop around nerve endings and consist primarily of Aβ oligomers, while the NFTs are intracellular lesions which develop in neuronal cell bodies and comprise primarily of aggregates of the microtubule (MT)-binding protein tau. Yet, recently it has been shown in vivo that Aβ binds to tau to form soluble stable complexes, and this binding can promote aggregation.3 Impor-tantly, the presence of both Aβ and tau cause a rapid dissociation of tau from the microtubules and a collapse of axonal structure— leading first to the malfunction of the synapses and ultimately t