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PSEN1 (1)
PSEN1 encodes presenilin-1, a subunit of γ-secretase, the aspartyl protease responsible for Aβ generation. More than 300 mutations in PSEN1 have been reported and mutations in PSEN1 are the most common cause of early onset Alzheimer's disease.
| Mutation | Clinical Phenotype |
Pathogenicity | Neuropathology | Biological Effect | Genomic Position | Genomic Region | Mutation Type Codon Change |
Research Models |
Primary Papers |
|---|---|---|---|---|---|---|---|---|---|
| E280A (Paisa) |
Alzheimer's Disease | AD : Pathogenic | 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. |
rs63750231 |
Exon 8 | Point, Missense GAA to GCA |
0 | Alzheimer's Disease Collaborative Group, 1995; Lopera et al., 1997; Lemere et al., 1996 |