Abstract: This invention provides methods and kits for the detection of tau-associated neurodegenerative diseases, such as Alzheimer's disease, prior to the onset of clinical symptoms. The method generally involves determining the amount of one or more tau protein isoforms in a biological sample relative to a suitable control, where an altered amount of the tau isoform(s) relative to the control identifies the presence of a tau-associated neurodegenerative disease. Such methods can also be applied more generally for the detection of tau abnormalities in any biological sample.