Neuropharmacology

QPS Austria Scientists Publish on Tau Hyperphosphorylation in Human Alzheimer’s Disease

Hyperphosphorylation of Tau is one of the major hallmarks of Alzheimer’s Disease pathology. However, the neurofibrillary tangles (NFTs) traditionally used in Braak & Braak clinical staging (1997) actually reflect the end-stage of paired helical filament (PHF) aggregations, which appear much earlier and are typically found in neuropil threads and not neuronal somata. PHF aggregations comprise a large array of variously phosphorylated Tau (pTau), with several phospho-sites closely associated with AD.

To expand upon current knowledge of the appearance, quantity and location of variously phosphorylated PHFs in specific brain regions at various stages of AD progression, the authors analyzed total human Tau, pThr231, pSer202, pTyr18 and ThioS positive tangles in four different cortical brain regions.

The study shows that Tau tangles are a rather late stage event, while the appearance of neuropil threads begins much earlier and is a better indication of progressive neuronal malfunction and neurodegeneration. Furthermore, it confirms the hippocampus as a more sensitive region for pTau accumulation than the cortex, especially for pTyr18 and pThr231 hyperphosphorylation.

Of the markers studied, the earliest measurable increase is in hippocampal pThr231 Tau. In the search for even earlier markers, the authors are planning future studies of stage C-terminal Tau markers, such as pSer396 or pSer422.

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