A recent study identified phosphorylation at serine-262 and serine-356 on tau protein as early biomarkers for Alzheimer's disease, suggesting their potential role in diagnosis and treatment

In the study, published in Nature Medicine, researchers analyzed Tris-buffered saline-soluble tau aggregates from autopsy-confirmed Alzheimer's disease brain tissues, identifying a core sequence spanning tau258–368. Phosphorylation at serine-262 and serine-356 was detected in prefibrillar tau aggregates of pre–neurofibrillary tangles (NFTs)

In contrast, antibodies against phosphorylation at serine-202/threonine-205 and threonine-231, located outside the soluble tau assemblies (STA) core, stained a broader range of tau aggregates, including mature NFTs, dystrophic neurites, and neuropil threads in the hippocampus.

A recombinant STA core peptide altered neuronal excitability and synaptic transmission in mouse hippocampal slices, suggesting involvement in Alzheimer's disease (AD) pathogenesis.

The researchers also developed a cerebrospinal fluid (CSF) assay to detect these phosphorylated tau species. The assay distinguished AD from non-AD tauopathies, correlating with NFT burden, cognitive decline, and tau PET uptake across Braak NFT stages.

"Together, our findings inform about the status of early-stage tau aggregation, reveal aggregation-relevant phosphorylation epitopes in tau and offer a diagnostic biomarker and targeted therapeutic opportunities for AD," said lead study author Tohidul Islam, of the Department of Psychiatry and Neurochemistry at the Institute of Neuroscience and Physiology at The Sahlgrenska Academy at the University of Gothenburg in Mölndal, Sweden, and colleagues.

The authors declared no competing interests.