Introduction
Materials and methods
Brain tissues
Diagnosis | Case no. | Sex | Age at death (year) | Duration (year) | Brain (g) | PMI (h) |
---|---|---|---|---|---|---|
PiD | 1 | F | 62 | 10 | 928 | N/A |
PiD | 2 | M | 56 | 10 | 1150 | N/A |
PSP | 3 | F | N/A | N/A | N/A | N/A |
PSP | 4 | F | 71 | 7 | 1070 | 8 |
PSP | 18 | M | 74 | 10 | 1265 | N/A |
PSP | 24 | M | 72 | 7 | 1290 | N/A |
PSP | 25 | F | 68 | 9 | 1250 | N/A |
PSP | 26 | M | 80 | 7 | 1060 | N/A |
CBD | 5 | F | 74 | N/A | 1010 | 7 |
CBD | 6 | F | 83 | 27 | 1024 | 8 |
CBD | 7 | F | 80 | 10 | 990 | 10 |
CBD | 17 | F | 65 | 5 | 950 | 2 |
CBD | 23 | M | 71 | 6 | 1250 | 0.5 |
CBD + PSP | 19 | M | 67 | 4 | 840 | 7 |
MAPT (+16) | 8 | M | 55 | 12 | 1240 | N/A |
MAPT (+16) | 9 | F | 65 | 13 | 1040 | N/A |
MAPT (+16) | 10 | M | 46 | 53 | 1240 | 18 |
MAPT (+13) | 11 | M | 70 | 5 | 1100 | 18 |
MAPT (+16) | 27 | M | 65 | 1 | N/A | 24 |
AD | 12 | M | 72 | 5 | 1240 | 2 |
AD | 13 | F | 72 | 6 | 1100 | 4 |
AD | 14 | F | 68 | 20 | 775 | 13 |
AD | 15 | M | 80 | N/A | 1390 | 7 |
AD | 16 | F | 70 | N/A | 1126 | 7 |
AD | 20 | F | 65 | 9 | 1165 | N/A |
AD | 21 | F | 76 | 13 | 950 | N/A |
AD | 22 | M | 56 | 4 | 1350 | 7 |
PiD | 28 | F | 58 | 8 | 1065 | N/A |
PiD | 29 | M | 77 | 4 | N/A | N/A |
PiD | 30 | M | 69 | 10 | 850 | N/A |
PSP | 31 | M | 88 | 6 | 1038 | 4.4 |
PSP | 32 | M | 85 | 15 | 850 | 1 |
PSP | 33 | M | 87 | 8 | 1120 | 15 |
CBD | 34 | F | 87 | 4 | 1026 | 36 |
CBD | 35 | M | 88 | 7 | 1025 | 15 |
CBD | 36 | F | 71 | 8 | 1020 | 7.5 |
MAPT (+16) | 37 | F | 63 | 15 | 1100 | 96 |
MAPT (+16) | 38 | M | 66 | N/A | N/A | N/A |
AD | 39 | M | 72 | 12 | 1251 | N/A |
AD | 40 | M | 62 | 8 | 1100 | 24 |
Antibodies used in this study
Preparation of sarkosyl-insoluble tau
In-gel digestion and nano-LC/MS/MS analysis
Expression and purification of recombinant wild-type and deletion mutant of human tau
Trypsin digestion of sarkosyl-insoluble tau and purification of trypsin-resistant tau
Protein sequence and mass spectrometric analyses of trypsin-resistant tau fragments
Immunoelectron microscopy
Results
Sarkosyl-insoluble C-terminal tau fragments in tauopathy brains
Trypsin-resistant tau banding patterns in tauopathy brains
Protein sequence and mass spectrometric analyses of trypsin-resistant tau in tauopathy brains
Tauopathy | Signal no. | Measured MS (AP−) | Measured MS (AP+) | Calculated MS +Na(22) | Assignment | 12E8(S262) | PHF1(pS396/404) | Apparent MW |
---|---|---|---|---|---|---|---|---|
AD | ① | – | 11,597.7 | 11,596.1 | 3R 268–406 | – | ○ | 15 |
② | – | 11,527.6 | 11,526.1 | 4R 299–406 | – | ○ | 15 | |
③ | 10,517.1 | 10,517.3 | 10,513.6 | 3R 268–395 | – | – | 12 | |
④ | 10,447.2 | 10,448.3 | 10,443.5 | 4R 299–395 | – | – | 12 | |
⑤ | 9403.2 | 9403.2 | 9400.0 | 3R 268–385 | – | – | 7 | |
⑥ | 9330.1 | 9330.1 | 9330.0 | 4R 299–385 | – | – | 7 | |
PiD | ① | 12,097.0 | 12,095.8 | 12,089.5 | 3R 243–387 | ○ | – | 12 |
② | 11,894.7 | 11,893.8 | 11,890.4 | 3R 243–385 | ○ | – | 12 | |
CBD | ① | 13,757.9 | 13,756.6 | 13,758.3 | 4R 268–395 | – | – | 15 |
② | 12,647.3 | 12,645.3 | 12,644.8 | 4R 268–387 | – | – | 13 | |
③ | 10,750.1 | 10,751.0 | 10,749.7 | 4R 268–369 | △ | – | 10 | |
PSP | ① | 14,599.7 | ND | 14,600.8 | 4R 260–395 | ○ | – | 16 |
② | 13,760.4 | ND | 13,758.3 | 4R 268–395 | – | – | 15 | |
③ | 13,569.1 | ND | 13,567.3 | 4R 243–369 | – | – | 15 | |
CBD + PSP | ① | 14,605.3 | ND | 14,600.8 | 4R 260–395 | – | △ | 16 |
② | 13,760.7 | ND | 13,758.3 | 4R 268–395 | – | △ | 15 | |
③ | 12,647.5 | ND | 12,644.8 | 4R 268–387 | – | – | 13 | |
④ | 10,751.1 | ND | 10,749.7 | 4R 268–369 | △ | – | 10 | |
MAPT
| ① | 15,685.11 + 80x4 | 15,684.7 | 15,683.3 | 4R 260–406 | ○ | ○ | 17 |
② | 14,603.9 | 14,603.8 | 14,600.8 | 4R 260–395 | ○ | – | 16 | |
③ | 13,761.4 | 13,760.3 | 13,758.3 | 4R 268–395 | – | – | 15 | |
④ | 12,647.7 | 12,647.3 | 12,644.8 | 4R 268–387 | – | – | 13 | |
⑤ | 11,594.0 | 11,596.2 | 11,592.2 | 4R 260–369 | ○ | – | 12 | |
⑥ | 10,751.5 | 10,751.2 | 10,749.7 | 4R 268–369 | – | – | 10 |