Table 2.
Mutations, described in TM-I domain of PSEN1. Majority of mutations were associated with relatively young onset and positive family history of disease.
| Mutation | Clinical Symptoms | Age of Onset (Year) |
Family History | Functional Studies | References |
|---|---|---|---|---|---|
| Val82Leu | EOAD | 53–58 | Positive (2 French family) |
HEK293: 1.5 times elevated Aβ42/Aβ40 CHO: 1.4 times reduced CHO-APP695 |
[20] |
| Ile83Thr | EOAD, behavioral symptoms, depression, hallucinations | 55–64 | Probable positive (Tunisian) |
NA | [22] |
| del_Ile83/Met84 | EOAD, spastic paraparesis, cotton wool plaques, cerebral amyloid antipathy | 34–38 | Positive (Scottish) |
HEK293: 4.8 times elevated Aβ42/Aβ40 H4: 2.6 times higher Aβ42/Aβ40 |
[24,25] |
| Met84Val | EOAD, psychotic symptoms | 49–57 | Positive (Italian) |
NA | [23,29] |
| Leu85Pro | EOAD, spastic paraparesis | 26 | De novo (Japan) |
HEK293: 1.9 times elevated Aβ42/Aβ40 | [16] |
| Pro88Leu | EOAD, myoclonus, Parkinsonism, apraxia | 20s | Unknown (China) |
Increased the long amyloid peptides | [17] |
| Val89Leu G>C |
EOAD | Late 30s | Unknown (China) |
NA | [24] |
| Val89>Leu G>T |
EOAD with personality changes | 46–51 | Familial (Spain) |
NA | [18] |
| Cys92Ser | EOAD, parkinsonism, hallucination | 49–70 | Familial (Italy) |
Fibroblast cells: elevated Aβ42 levels | [26] |
| Val94Met | EOAD | 53 | De novo (Columbia) |
NA | [30] |
| Val96Phe | EOAD | 44–57 | Familial (Japan, Malaysia) |
elevated Aβ42/totalAβ in COS1 cells | [8,13], our case |
| Val97Leu | EOAD | Late 30s, early 40s | Familial (China) |
SH-SY5Y cells: elevated intracellular and extracellular Aβ42 | [19,27] |
| Thr99Ala | EOAD | 43 | De novo (Japan) |
NA | [21] |