Table 1.
Studied FAD-linked PSEN1 mutations, their location in PSEN1/GSEC and reported ages at AD onset (AAOs).
| PSEN1 mutation | Position | Mean AAO (range) | # in Fig. 2B |
|---|---|---|---|
| L166P | TMD 3 | 23.5 (23–24) | 1 |
| M233V | TMD 5 | 24.8 (15–34) | 2 |
| M233I | TMD 5 | 27 (24–30) | 3 |
| L381F | TMD 7 | 29.8 (28–32) | 4 |
| I143T | TMD 2 | 31.9 (28–38) | 5 |
| L235P | TMD 5 | 32.5 (29–39) | 6 |
| G384A | TMD 7 | 36.0 (26–45) | 7 |
| R278T | TMD 6 | 37.0 | 8 |
| Y115H | Loop 1 | 37.0 (30–47) | 9 |
| L166R | TMD 3 | 37.3 (32–44) | 10 |
| L171P | TMD 3 | 38 (36–40) | 11 |
| A431E | IC loop | 39.4 (36–53) | 12 |
| M139V | TMD 2 | 39.9 (32–48) | 13 |
| Ins113T (intron 4) | Loop 1 | 42.1 (35–45) | 14 |
| L282R | IC loop | 43.8 (35–50) | 15 |
| G266S | TMD 6 | 45.0 (33–45) | 16 |
| M139T | TMD 2 | 47.3 (39–51) | 17 |
| L235V | TMD 5 | 47.4 (44–59) | 18 |
| E280A | IC loop | 48.1 (46–52) | 19 |
| F105C | Loop 1 | 48.6 (45–51) | 20 |
| V89L | TMD 1 | 48.7 (38–51) | 21 |
| A246E | TMD 6 | 49.1 (40–66) | 22 |
| I143F | TMD 2 | 55.0 (51–59) | 23 |
| R269H | TMD 6 | 56.4 (50–62) | 24 |
| A79V | TMD 1 | 60.6 (53–78) | 25 |
| R35Q | N-term | — | — |
| E318G | IC loop | — | — |
AAOs were defined accordingly to the Alzforum PSEN1 mutation database (https://www.alzforum.org/mutations/psen-1), AD&FTD mutation database from the University of Antwerp (https://www.molgen.ua.ac.be/admutations) and the available literature [65]. R35Q and E318G substitutions were selected as non-pathogenic.
Ins113T p. L113-I114InsT, TMD transmembrane domain, Loop 1 extracellullar loop between TMD1-2, IC loop intracellular loop between TMD 6-7, N-term N-terminal region.