Mutations Position Table
APP A673 Mutations
| Mutation | Pathogenicity | DNA Change | Expected RNA | Protein Consequence | Coding/Non-Coding | Genomic Region | Neuropathology | Biological Effect | Primary Papers |
|---|---|---|---|---|---|---|---|---|
| A673T (Icelandic) |
AD : Protective | Substitution | Substitution | Missense | Coding | Exon 16 | This variant is associated with minimal amyloid deposition. In three carriers, biopsies showed no Aβ, phospho-tau, or p62 pathology. Low sAPPβ and Aβ42 in CSF. |
Shifts APP processing towards non-amyloidogenic pathway, making APP a less-favorable substrate for β-secretase, resulting in less Aβ production. Also, Aβ peptides less prone to aggregation. Mutant Aβ peptides may have neuroprotective properties. |
Peacock et al., 1993; Jonsson et al., 2012 |
| A673V |
AD : Not Classified | Substitution | Substitution | Missense | Coding | Exon 16 | Definite AD by CERAD criteria, with extensive deposition of Aβ and tau pathology (Braak stage VI). Cerebral amyloid angiopathy. Deposits contained high levels of Aβ40 and were noted to be unusually large, with few preamyloid deposits. Localization was frequently perivascular. |
In vitro, A673V shifts β-secretase processing of APP toward the amyloidogenic pathway and may increase Aβ aggregation; however, co-incubation of mutant and wild-type Aβ inhibits amyloidogenesis and toxicity. |
Di Fede et al., 2009 |
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