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Table 2 Different types of tau species that have shown seeding ability

From: What is the evidence that tau pathology spreads through prion-like propagation?

Tau species Derived from seeding assay Noteworthy features Ref
P301S tau tg brain derived sarkosyl insoluble tau
Recombinant P301S aggregates
P301S tau transgenic mouse brain (at symptomatic stages of disease)
Heparin induced in vitro aggregation
Cell based P301S tau aggregation assay wherein insoluble tau inclusions formed within cells and were visualised by light microscopy and verified using biochemical insolubility assays.
Sarkosyl insoluble P301S tau aggregates enriched in 30-50% sucrose fractions were verified by EM
1. Sarkosyl insoluble P301S tau from mouse brain has greater seeding capacity than total brain homogenate from P301S transgenic mice. [45]
2. Native (sarkosyl insoluble) P301S tau from mouse brain has greater seeding competence than recombinant P301S tau aggregates [45]
3. In vitro phosphorylation of recombinant P301S tau seeds does not increase their seeding competence. [45]
4. Seeding capacity of recombinant P301S tau becames equivalent to that of sarkosyl insoluble P301S tau from tg mouse brain when incubated with it in vitro. [45]
5. Sarkosyl insouble P301S tau from tg mouse brain separates into 30-50% sucrose fractions and comprises of AT8 and AT100 positive 6-10mer tau oligomers and short tau fibrils [79]
AD brain derived sarkosyl soluble and insoluble tau Fresh frozen AD brain homogenate (Braak stages 1-3) FRET based cellular aggregation of CYP/RFP-tagged P301S-RD tau 1. In a significant number of cases, there was no biochemically evident insoluble tau (Braak stages 1-3) but the brain homogenates displayed strong seeding ability. [48]
Recombinant P301S-RD tau oligomers and short fibrils Heparin induced in vitro aggregation Split luciferase based cellular aggregation of NLuc and Cluc-tagged P301S-RD tau 1. Tau trimers were smallest seed competent tau oligomers [93]
AD brain derived tau oligomers Fresh frozen AD brain Split luciferase based cellular aggregation of NLuc and Cluc-tagged P301S-RD tau 1. Though tau oligomers extracted from AD brain ranging in size from n = 1 to n > 20, only oligomers equal to or greater than n = 3 exhibited seeding ability. [93]
P301S tau tg brain derived undefined pathological tau species P301S tau tg mouse brain homogenates
(at pre-symptomatic and symptomatic stages)
FRET based cellular aggregation of CYP/RFP-tagged P301S-RD tau 1. Seeding activity detected as early as 1 month of age prior to emergence of misfolding (MC1 immunoreactivity which emerged at 3 m) or hyperphosphorylation (AT8 immunoreactivity which emerged at 6 m) [71]
Recombinant RD-tau “strains” of distinct morphologies Exposure of stably transfected cells expressing YFP-tagged P301L/V337M-RD tau to recombinant tau fibrils led to emergence of morphologically distinct tau inclusions; colonies of cells with the same inclusion were amplified and the relevant tau inclusion was stably propagated in a clonal fashion Induction of morphologically distinct fluorescent accumulates of RD-tau evident by light microscopy following exposure to tau seed 1. Morphologically distinct tau strains were evident with different aggregation propensities and seeding abilities
2. Tau strains propagated morphologically distinct inclusions stably in cell culture and in vivo through successive generations
[112]
Recombinant 2N4R tau seeds Sarkosyl insoluble AD brain tau Repetitive self seeded fibrilisation of recombinant 2N4R tau in vitro led to progressive increase in insoluble tau fibrils verified by EM
AD-tau seed induced fibrillisation of recombinant 2N4R tau in vitro verified by EM
Induction of tau inclusions in rodent neurones NOT expressing exogenous human tau following exposure to tau seed
Induction of tau inclusions in rodent neurones NOT expressing exogenous human tau following exposure to tau seed
1. Seeds derived from human AD brain (and therefore comprising of wild-type human tau) capable of inducing aggregation of wild-type rodent tau at physiological expression levels.
2. Induction of aggregation in cells verified by biochemical insolubility assays
3. Sarkosyl insoluble AD tau more seed competent than recombinant tau seeds generated in vitro but former able to confer its higher seeding competence to latter if seeded with it.
[65]
  1. Tau seeds capable of inducing aggregation of soluble tau have been generated from recombinant tau in vitro, from cells stably transfected with tau fragments, from brains of transgenic mice, and from AD patients. This table lists some of these seeds from selected publications