Title

Pathological conformations involving the amino terminus of tau occur early in Alzheimer's disease and are differentially detected by monoclonal antibodies.

Journal

Neurobiology of disease

Volume

94

Issue

None

Pages

18-31

Date

2016-10-01

Authors

Combs B | Hamel C | Kanaan NM

Previously, we have shown that TNT1 is a marker of PAD exposure and that this event occurs early in the progression of Alzheimer’s disease. Establishing whether this was true for all N-terminal antibodies was important for understanding more about PAD exposure in Alzheimer’s disease. We significantly extend these findings with TNT1 and show that TNT2 behaves similarly as a marker of PAD exposure. In contrast, other N-terminal antibodies, with slightly different epitopes, do not function as pathological, PAD exposure-specific markers and recognize all forms of tau similarly. Here, we found that TNT1 and TNT2 appear in Braak I–II stages and do not colocalize with ThR in the diffuse, granular pre-tangle pathology conclusively demonstrating that PAD exposure is an early event.

Apparent ThR-positive ghost tangles (i.e., without nuclei (Braak et al., 1994)) are no longer labeled by TNT1 or TNT2, which confirms that PAD exposure is lost in the latest stages of NFT evolution.

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