This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (20)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Genetic Counseling/ Testing/ Therapy  • Alzheimer Disease  • Neurogenetics  • Alert me on articles by topic

Karin Axelman, RNT; Hans Basun, MD, PhD; Lars Lannfelt, MD, PhD

Arch Neurol. 1998;55:698-702.

Objectives  To describe clinical and genealogical data of a Swedish family with a His163Tyr mutation in the presenilin-1 gene (PS1) and to study the Alzheimer disease (AD) penetrance in this family.

Design  Interviews with relatives, studies of medical records, analysis of pedigree, physician examination of the affected individuals, and comparison with other families affected by AD with PS1 mutations.

Setting  Large university-affiliated hospital.

Patients and Other Participants  Individuals with a His163Tyr mutation in PS1 and their relatives.

Results  A study of this family with a history of very early AD onset (mean age, 47 years) has been previously published, but an investigation of the extended family revealed a new pattern of onset, with a mean age at onset of 54 years (range, 44-65 years). In general, families with AD show a tight cluster of age at onset with high penetrance of the disease. However, in this family, an individual whose child carries the PS1 mutation died at age 67 years free from cognitive symptoms, indicating a very late age at onset or nonpenetration of the disease. No association between age at onset and disease duration was found. Furthermore, the disease duration did not differ between those having an early onset compared with those having a late onset. The earliest clinical manifestations were deficits in memory function and disorientation in time and place. Myoclonic jerks and epileptic seizures were common symptoms later in the disease.

Conclusion  The large range in age at onset in this family with a uniform genetic basis for the disease, a His163Tyr mutation in PS1, supports the existence of other unknown genetic or environmental factors of importance for the expression of the AD phenotype.

From the Karolinska Institute, Alzheimer's Disease Research Center, Department of Clinical Neuroscience and Family Medicine, Huddinge University Hospital, Huddinge, Sweden.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

A unique gene expression signature discriminates familial Alzheimer's disease mutation carriers from their wild-type siblings
Nagasaka et al.
Proc. Natl. Acad. Sci. USA 2005;102:14854-14859.
ABSTRACT | FULL TEXT  

Clinical, Pathological, and Biochemical Spectrum of Alzheimer Disease Associated With PS-1 Mutations
Lleo et al.
AJGP 2004;12:146-156.
ABSTRACT | FULL TEXT  

Genetic background regulates {beta}-amyloid precursor protein processing and {beta}-amyloid deposition in the mouse
Lehman et al.
Hum Mol Genet 2003;12:2949-2956.
ABSTRACT | FULL TEXT  

Early onset familial Alzheimer's disease: Mutation frequency in 31 families
Janssen et al.
Neurology 2003;60:235-239.
ABSTRACT | FULL TEXT  

Autopsy-Confirmed Familial Early-Onset Alzheimer Disease Caused by the L153V Presenilin 1 Mutation
Janssen et al.
Arch Neurol 2001;58:953-958.
ABSTRACT | FULL TEXT  

Novel Presenilin 1 Mutations Associated With Early Onset of Dementia in a Family With Both Early-Onset and Late-Onset Alzheimer Disease
Devi et al.
Arch Neurol 2000;57:1454-1457.
ABSTRACT | FULL TEXT  

A presenilin 1 mutation (Ser169Pro) associated with early-onset AD and myoclonic seizures
Ezquerra et al.
Neurology 1999;52:566-566.
ABSTRACT | FULL TEXT