Mutations Position Table
PSEN1 L282 Mutations
| Mutation | Pathogenicity | DNA Change | Expected RNA | Protein Consequence | Coding/Non-Coding | Genomic Region | Neuropathology | Biological Effect | Primary Papers |
|---|---|---|---|---|---|---|---|---|
| L282P |
AD : Not Classified | Substitution | Substitution | Missense | Coding | Exon 8 | Unknown, but in one patient, MRI revealed mild, diffuse cortical atrophy, and FDG-PET showed severe, bilateral hypometabolism in parietal and temporal cortices. |
Unknown, but multiple in silico algorithms predicted damaging |
Kim et al., 2020 |
| L282R |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 8 | Neuropathology consistent with Alzheimer's disease. |
Decreased Aβ (37 + 38 + 40) / (42 + 43) and Aβ37/Aβ42 ratios and increased Aβ43. The Aβ42/Aβ40 ratio was increased or unchanged. |
Aldudo et al., 1998 |
| L282F |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 8 | Unknown; MRI showed mild medial temporal atrophy. FDG-PET showed glucose hypometabolism in the bilateral parietal cortices and posterior cingulate gyri. |
Although Aβ42/Aβ40 was similar to controls, Aβ37/Aβ42 was decreased and Aβ43 levels were increased in a cell-based assay. |
Hamaguchi et al., 2009 |
| L282V |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 8 | Extensive neurofibrillary tangles and amyloid deposits including both dense-cored plaques and diffuse plaques. Severe cerebral amyloid angiopathy (CAA) in the neocortex, hippocampus, and cerebellum. CAA deposits associated with dystrophic neurites and inflammatory gliosis. Severe white-matter loss. Cerebellar amyloid pathology associated with severe CAA and loss of Purkinje cells. |
Increased Aβ42/Aβ40 ratio and decreased Aβ37/Aβ42 ratio in cells. In vitro, Aβ42 and Aβ40 production, as well as Aβ42/Aβ40 ratio, similar to wild-type. Impairs trafficking of the APOE receptor apoER2. |
Dermaut et al., 2001 |
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