Table 2.
Tau fragments identified in human brain that may be involved in human tauopathies
| Tau fragment | Amino acid residues | Mr (kDa) | Comments | References |
|---|---|---|---|---|
| C-terminally cleaved tau | M1- | 40–53 | Present in synaptosomes from AD brain C terminus not identified |
[459] |
| Delta tau | H14/A15-D421 | Associates with tangles in AD brain Identified in the brains of aged wild-type and transgenic 3xTg-AD and htau mice, which develop tangles, amyloid plaques and synaptic dysfunction. Induces tau filament formation and inversely correlates with cognitive function. Induced by Aβ in neurons and leads to apoptosis. Tau is cleaved at D13 by caspase-6 and at D421 by caspase-3 |
[30, 125, 151, 182, 208, 330, 369, 412] | |
| NH2-tau | Q26-R230 | Enriched in synaptosomal mitochondria in AD brain Induced by apoptosis in SHSY-5Y neuroblastoma cells. Present in hippocampus in AD11 transgenic mice which have chronic NGF deprivation during adulthood and display AD-like molecular and behavioural phenotypes |
[7–10, 24, 89, 90, 404] | |
| E45-R230 | 17 | Detected in AD, ALS, and control brain Generated in neurons by exposure to Aβ or by thapsigargin-mediated inhibition of autophagy. Induces neurodegeneration when expressed in mice. Not toxic when expressed in N2a or CHO cells, or neurons Generated by calpain-1 cleavage See related fragment A125-R230 below |
[152, 271, 384, 414, 493] | |
| S129-(S71 in 0N3R tau) | 33 | Isolated from tangles in AD brain Decreased ability to bind to tubulin. C terminus not identified |
[364] | |
| Q124-L441 | 43 | Present in human brain Increased acetylation and detyrosination of tubulin when expressed in N1E-115 neuroblastoma cells |
[109] | |
| A125-R230 | 17 | Present in AD and control brain Not toxic when expressed in N2a or CHO cells, or neurons. Generated by calpain-2 cleavage See related fragment E45-R230 above |
[152] | |
| I151-A391 | 29 | Present in the neurofibrillary tangle core in AD brain Expression of either 3R tau151–391 (lacking 275–305) or 4R tau151–391 in transgenic rats induces tangle formation. Muscle weakness develops only in 4R tau151–391 rats |
[132, 331, 373, 542] | |
| Tau35 | E187-L441 | 33–37 | Present in AGD, PSP, and CBD, but not control brain Includes four microtubule binding repeats. Expression of Tau35 mice in transgenic mice induces tau pathology, cognitive and motor dysfunction |
[16, 42, 216, 520] |
| Tau-CTF24 | L243-L441 | 24 | 20–28 kDa C-terminal tau species detected in AD, CBD, PSP, and FTLD-tau, but not control brain Includes four microtubule binding repeats. Present in Tg601 mice which exhibit increased tau phosphorylation and synapse loss |
[327] |
Tau fragments that have been detected in human brain that is potentially associated with the development of tauopathy. The tau cleavage products are listed in order of their most N-terminal amino acid (single letter code). 3xTg-AD mice are transgenic for mutant forms of tau, amyloid precursor protein, and presenilin 1 [377]; AD11 mice are transgenic for NGF antibodies [63]; Tau35 mice are transgenic for the wild-type human tau fragment E187-L441 [42]; Tg601 mice are transgenic for wild-type 2N4R tau [240]
3R tau isoforms containing three microtubule binding repeats, 4R tau isoforms containing four microtubule binding repeats, Aβ amyloid-β peptide, AD Alzheimer’s disease, AGD argyrophilic brain disease, ALS amyotrophic lateral sclerosis, CBD corticobasal degeneration, CHO Chinese hamster ovary, FTLD frontotemporal lobar degeneration, PSP progressive supranuclear palsy