Pathogenicity: Alzheimer's Disease : Pathogenic, Dementia with Lewy Bodies : Unclear Pathogenicity
Clinical Phenotype: Alzheimer's Disease, Dementia with Lewy Bodies
Reference Assembly: GRCh37 (105)
Position: Chr1:227071518 C>T
dbSNP ID: rs63750048
Coding/Non-Coding: Coding
Genomic Region: Exon 4
Mutation Type: Point, Missense
Codon Change: GCG to GTG


This mutation was identified in a three-generation Sardinian kindred. There was considerable variability in the clinical presentation within the family, with diagnoses of Alzheimer's disease as well as dementia with Lewy bodies. The A85V mutation is associated with a complex phenotype characterized by dementia with parkinsonism, a relatively late onset (60 to 71 years), and a long duration (22 and 25 years). The mutation is thought to be pathogenic; all mutation carriers (except one young individual thought to be presymptomatic) developed AD, dementia with Lewy bodies, or both. Moreover, the A85V mutation was absent in 211 unrelated individuals from the same Sardinian population (Piscopo et al., 2008).


Neuropathologic data are available for the proband. In the neocortex amyloid deposition, neurofibrillary changes and diffuse Lewy bodies were observed. Neuroimaging in two patients showed bilateral basal ganglia calcifications (Piscopo et al., 2008).

Biological Effect



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Paper Citations

  1. . A novel PSEN2 mutation associated with a peculiar phenotype. Neurology. 2008 Apr 22;70(17):1549-54. PubMed.

Further Reading

Learn More

  1. Alzheimer Disease & Frontotemporal Dementia Mutation Database

Protein Diagram

Primary Papers

  1. . A novel PSEN2 mutation associated with a peculiar phenotype. Neurology. 2008 Apr 22;70(17):1549-54. PubMed.


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