Tau seeding in cases of multiple sclerosis.
Michael S LaCroixHilda MirbahaPing ShangStephanie ZandeeChan FoongAlexandre PratCharles L WhiteOlaf StuveMarc I DiamondPublished in: Acta neuropathologica communications (2022)
Relapsing remitting multiple sclerosis (MS) is an inflammatory demyelinating disorder of the central nervous system that in many cases leads to progressive MS, a neurodegenerative disease. Progressive MS is untreatable and relentless, and its cause is unknown. Prior studies of MS have documented neuronal accumulation of phosphorylated tau protein, which characterizes another heterogeneous group of neurogenerative disorders, the tauopathies. Known causes of tauopathy are myriad, and include point mutations within the tau gene, amyloid beta accumulation, repeated head trauma, and viral infection. We and others have proposed that tau has essential features of a prion. It forms intracellular assemblies that can exit a cell, enter a secondary cell, and serve as templates for their own replication in a process termed "seeding." We have previously developed specialized "biosensor" cell systems to detect and quantify tau seeds in brain tissues. We hypothesized that progressive MS is a tauopathy, potentially triggered by inflammation. We tested for and detected tau seeding in frozen brain tissue of 6/8 subjects with multiple sclerosis. We then evaluated multiple brain regions from a single subject for whom we had detailed clinical history. We observed seeding outside of MS plaques that was enriched by immunopurification with two anti-tau antibodies (HJ8.5 and MD3.1). Immunohistochemistry with AT8 and MD3.1 confirmed prior reports of tau accumulation in MS. Although larger studies are required, our data suggest that progressive MS may be considered a secondary tauopathy.
Keyphrases
- multiple sclerosis
- white matter
- cerebrospinal fluid
- single cell
- mass spectrometry
- cell therapy
- stem cells
- gene expression
- emergency department
- gold nanoparticles
- cerebral ischemia
- palliative care
- binding protein
- genome wide
- quantum dots
- systemic lupus erythematosus
- brain injury
- blood brain barrier
- big data
- functional connectivity
- electronic health record
- label free