Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
Position: Chr14:73653567 C>T
dbSNP ID: rs63749885
Coding/Non-Coding: Coding
Genomic Region: Exon 5
Mutation Type: Point, Missense
Codon Change: CAT to TAT


This mutation has been identified in a Swedish family known as Swed2. Originally eight affected individuals were reported over three generations, with memory difficulties beginning at age 47 on average (Clark et al., 1995). A follow-up study described the clinical details of this family in greater depth and published an extended pedigree with 101 individuals over six generations, 18 of whom were affected by dementia. Clinical data were available for 16 of the 18 affected family members and revealed that disease onset in this family was particularly variable, ranging from 44 to 65 years (mean: 54 years, n=16). Variability was also noted in disease duration (five to 23 years) and age at death (55 to 83 years). A commonality among affected individuals was insidious memory loss as the primary presenting feature. Psychiatric problems were also common, and myoclonic jerks and epileptic seizures occurred later in 10 of 16 patients. The mode of inheritance was consistent with autosomal-dominant inheritance in this family; however, one obligate carrier died at age 67 unaffected by dementia. Whether this was due to incomplete penetrance or a very late onset is unknown (Axelman et al., 1998).


The neuropathology associated with this mutation is unknown. Cerebral glucose metabolism may be affected early, as FDG-PET imaging showed that young, presymptomatic H163Y carriers had decreased glucose metabolism, especially in the thalamus, many years prior to the development of clinical symptoms of AD (Schöll et al., 2011).

Biological Effect

Increased Aβ42/Aβ total ratio when expressed in COS-1 cells co-transfected with APP695 (Murayama et al., 1999).


No Available Comments

Make a Comment

To make a comment you must login or register.


Paper Citations

  1. . The structure of the presenilin 1 (S182) gene and identification of six novel mutations in early onset AD families. Nat Genet. 1995 Oct;11(2):219-22. PubMed.
  2. . Wide range of disease onset in a family with Alzheimer disease and a His163Tyr mutation in the presenilin-1 gene. Arch Neurol. 1998 May;55(5):698-702. PubMed.
  3. . Glucose metabolism and PIB binding in carriers of a His163Tyr presenilin 1 mutation. Neurobiol Aging. 2011 Aug;32(8):1388-99. PubMed.
  4. . Enhancement of amyloid beta 42 secretion by 28 different presenilin 1 mutations of familial Alzheimer's disease. Neurosci Lett. 1999 Apr 9;265(1):61-3. PubMed.

Further Reading

Learn More

  1. Alzheimer Disease & Frontotemporal Dementia Mutation Database

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.

Primary Papers

  1. . The structure of the presenilin 1 (S182) gene and identification of six novel mutations in early onset AD families. Nat Genet. 1995 Oct;11(2):219-22. PubMed.

Other mutations at this position