Seed‐competent high‐molecular‐weight tau species accumulates in the cerebrospinal fluid of Alzheimer's disease mouse model and human patients

• DOI: 10.1002/ana.24716
• Publication Date: 2016-06-28T23:07:02Z
• Authors: Shuko Takeda; Caitlin Commins; Sarah L. DeVos; Chloe K. Nobuhara; Susanne Wegmann; Allyson D. Roe; Isabel Costantino; Zhanyun Fan; Samantha B. Nicholls; Alexis E. Sherman; Ana T. Trisini Li...; Clemens R. Scherzer; George A. Carlson; Rose Pitstick; Elaine R. Peskind; Murray A. Raskind; Ge Li; Thomas J. Montine; Matthew P. Frosch; Bradley T. Hyman
• Keywords: Tau protein

Cerebrospinal fluid (CSF) tau is an excellent surrogate marker for assessing neuropathological changes that occur in Alzheimer's disease (AD) patients. However, whether the elevated AD CSF just a of neurodegeneration or, fact, part process uncertain. Moreover, it unknown how relates to recently described soluble high-molecular-weight (HMW) species found postmortem brain and can be taken up by neurons seed aggregates.We have examined seeding uptake properties extracellular from various sources, including interstitial (ISF) transgenic mouse model ventricular antemortem lumbar patients.We ISF cells induce intracellular aggregates. Ventricular patients contained rare HMW exerted higher activity. Notably, was also detected patients, its levels were significantly compared control subjects. derived competent vitro.These findings suggest contains potentially bioactive species, giving new insights into role biomarker development AD. Ann Neurol 2016;80:355-367.