Neurofibrillary tangles, composed of insoluble aggregates of the microtubule-associated
protein Tau, are a pathological hallmark of Alzheimer disease (AD) and other tauopathies.
However, recent evidence indicates that neuronal dysfunction precedes the formation of
these insoluble fibrillar deposits, suggesting that earlier prefibrillar Tau aggregates may be
neurotoxic. To determine the composition of these aggregates, we have employed a
photochemical cross-linking technique to examine intermolecular interactions of full-length …