Mutations Position Table
PSEN1 E280 Mutations
| Mutation | Pathogenicity | DNA Change | Expected RNA | Protein Consequence | Coding/Non-Coding | Genomic Region | Neuropathology | Biological Effect | Primary Papers |
|---|---|---|---|---|---|---|---|---|
| E280A (Paisa) |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 8 | Neuropathology consistent with AD. Aβ42 abundant in the cerebral cortex, hippocampus, cerebellum, midbrain, and basal ganglia. Frequent CAA and cerebellar damage including ubiquitin–positive plaques, reactive astrocytes, and dystrophic neurites. Lewy body disease and TDP-43 pathology. Also, small vessel disease, disrupted gliovascular units, hyper-reactive astrocytes, and olfactory system alterations. |
In cells, increased the Aβ42/Aβ40 ratio and decreased the Aβ (37 + 38 + 40) / (42 + 43) and Aβ37/Aβ42 ratios. Activation of chaperone-mediated autophagy. Deleterious effects on stress vulnerability with increased tau phosphorylation, and impairment of sodium channels, calcium homeostasis, mitochondrial function, AChE activity. |
Alzheimer's Disease Collaborative Group, 1995; Lopera et al., 1997; Lemere et al., 1996 |
| E280G |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 8 | Frequent cotton-wool plaques and vascular amyloid deposits; Some cases with white-matter abnormalities and degeneration of the corticospinal tract. |
Increased Aβ42/Aβ40 ratio in cells and in vitro. Aβ42 secretion was increased in cells, but production of both Aβ42 and Aβ40 was reduced in vitro, as was endoproteolytic processing of PSEN1. |
Alzheimer's Disease Collaborative Group, 1995; O'Riordan et al., 2002 |
| E280K |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 8 | Unknown; MRI showed generalized brain atrophy, including atrophy of the hippocampus. |
Unknown; predicted probably damaging in silico. |
Ch'ng et al., 2015 |
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