Mutations Position Table

APP K687 Mutations

Tools

Back to the Top
Mutation Pathogenicity DNA Change Expected RNA | Protein Consequence Coding/Non-Coding Genomic Region Neuropathology Biological Effect Primary
Papers
K687N (A>C)
 AD : Likely Pathogenic Substitution Substitution | Missense Coding Exon 16

Unknown, but MRI showed brain atrophy and PET showed cortical amyloid accumulation. CSF biomarkers were consistent with AD.

Unknown, but K687N (A>T) increased Ab40 and Ab42, and when mixed with wildtype Ab, generated large oligomers; highly toxic in cells. Reduced degradation by neprilysin.

 Liang et al., 2023
K687N (A>T)
 AD : Not Classified Substitution Substitution | Missense Coding Exon 16

Unknown; MRI showed mild global brain atrophy without focal or vascular lesions. CSF biomarker profile consistent with AD, specifically elevated total tau and phosphorylated tau, along with reduced levels of Aβ1-42.

Reduces APP cleavage by α-secretase. Reduced production of total sAPP and especially sAPPα. Increased Aβ40 and Aβ42. Alone, mutant Aβ was less toxic to neuroblastoma cells than wild-type Aβ42, but mixed in equimolar amounts with wild-type, toxicity increased. Alone, mutant Aβ formed predominantly low-n oligomers in vitro, but mixed with wild-type Aβ, it aggregated into high-n oligomers.

 Kaden et al., 2012
K687Q
 AD : Pathogenic Substitution Substitution | Missense Coding Exon 16

Unknown, but imaging revealed white matter hyperintensities.

Increased nucleation of Aβ aggregation in yeast cell-based assay.

 Jiang et al., 2019;
Yi et al., 2020

Disclaimer: Alzforum does not provide medical advice. The Content is for informational, educational, research and reference purposes only and is not intended to substitute for professional medical advice, diagnosis or treatment. Always seek advice from a qualified physician or health care professional about any medical concern, and do not disregard professional medical advice because of anything you may read on Alzforum.