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Early-onset Alzheimer disease in families with late-onset Alzheimer disease: a potential important subtype of familial Alzheimer disease.
Arch Neurol. 2006 Sep; 63(9):1307-11.AN

Abstract

BACKGROUND

Genetic influences on the development of late-onset Alzheimer disease (LOAD) are heterogeneous and ill defined.

OBJECTIVE

To determine the genetic risk factors for LOAD.

DESIGN

We asked the following questions: (1) Does early-onset Alzheimer disease (EOAD) occur in families with predominantly LOAD? and (2) Does the apolipoprotein E (APOE) genotype explain the wide differences in onset age in LOAD families?

SETTING

University of Washington Alzheimer Disease Research Center, Seattle.

PARTICIPANTS

A total of 136 kindreds and a separate group of 29 affected parent-child pairs.

MAIN OUTCOME MEASURES

We evaluated the kindreds with familial LOAD for the occurrence of EOAD and the affected parent-child pairs with a 20-year or more difference in the age at onset.

RESULTS

In the 136 kindreds with LOAD, 104 had only late-onset cases (men, 36%), whereas 32 families (24%) had a combination of LOAD and EOAD cases. The 44 EOAD cases in these families accounted for 20% of cases of AD in the 32 families and 6% in all 136 families. The early-onset cases had a mean +/- SD onset age of 56.1 +/- 3.2 years (range, 45-59 years; men, 50%). Seven (28%) of 25 individuals with EOAD sampled did not have an APOE epsilon4 allele, and 2 of the earliest-onset cases were epsilon3/epsilon3. In 29 parent-child pairs with a 20-year or more difference in age at onset, 7 (35%) of the 20 children sampled did not have an APOE epsilon4 allele.

CONCLUSIONS

Many LOAD families (approximately 25%) have at least 1 individual with EOAD, and in these individuals, the ratio of men to women is nearly 50%, suggesting a possible subtype of familial AD. The APOE genotype plays an important role in these early-onset cases, but at least one fourth of the risk must represent the influence of other genetic and/or environmental factors. These LOAD families with early-onset cases represent an important resource for investigation of these factors.

Authors+Show Affiliations

Department of Neurology, VA Puget Sound Health Care System, University of Washington, 1660 S. Columbian Way, Seattle, WA 98108, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

16966510

Citation

Brickell, Kiri L., et al. "Early-onset Alzheimer Disease in Families With Late-onset Alzheimer Disease: a Potential Important Subtype of Familial Alzheimer Disease." Archives of Neurology, vol. 63, no. 9, 2006, pp. 1307-11.
Brickell KL, Steinbart EJ, Rumbaugh M, et al. Early-onset Alzheimer disease in families with late-onset Alzheimer disease: a potential important subtype of familial Alzheimer disease. Arch Neurol. 2006;63(9):1307-11.
Brickell, K. L., Steinbart, E. J., Rumbaugh, M., Payami, H., Schellenberg, G. D., Van Deerlin, V., Yuan, W., & Bird, T. D. (2006). Early-onset Alzheimer disease in families with late-onset Alzheimer disease: a potential important subtype of familial Alzheimer disease. Archives of Neurology, 63(9), 1307-11.
Brickell KL, et al. Early-onset Alzheimer Disease in Families With Late-onset Alzheimer Disease: a Potential Important Subtype of Familial Alzheimer Disease. Arch Neurol. 2006;63(9):1307-11. PubMed PMID: 16966510.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Early-onset Alzheimer disease in families with late-onset Alzheimer disease: a potential important subtype of familial Alzheimer disease. AU - Brickell,Kiri L, AU - Steinbart,Ellen J, AU - Rumbaugh,Malia, AU - Payami,Haydeh, AU - Schellenberg,Gerard D, AU - Van Deerlin,Vivianna, AU - Yuan,Wuxing, AU - Bird,Thomas D, PY - 2006/9/13/pubmed PY - 2006/10/19/medline PY - 2006/9/13/entrez SP - 1307 EP - 11 JF - Archives of neurology JO - Arch. Neurol. VL - 63 IS - 9 N2 - BACKGROUND: Genetic influences on the development of late-onset Alzheimer disease (LOAD) are heterogeneous and ill defined. OBJECTIVE: To determine the genetic risk factors for LOAD. DESIGN: We asked the following questions: (1) Does early-onset Alzheimer disease (EOAD) occur in families with predominantly LOAD? and (2) Does the apolipoprotein E (APOE) genotype explain the wide differences in onset age in LOAD families? SETTING: University of Washington Alzheimer Disease Research Center, Seattle. PARTICIPANTS: A total of 136 kindreds and a separate group of 29 affected parent-child pairs. MAIN OUTCOME MEASURES: We evaluated the kindreds with familial LOAD for the occurrence of EOAD and the affected parent-child pairs with a 20-year or more difference in the age at onset. RESULTS: In the 136 kindreds with LOAD, 104 had only late-onset cases (men, 36%), whereas 32 families (24%) had a combination of LOAD and EOAD cases. The 44 EOAD cases in these families accounted for 20% of cases of AD in the 32 families and 6% in all 136 families. The early-onset cases had a mean +/- SD onset age of 56.1 +/- 3.2 years (range, 45-59 years; men, 50%). Seven (28%) of 25 individuals with EOAD sampled did not have an APOE epsilon4 allele, and 2 of the earliest-onset cases were epsilon3/epsilon3. In 29 parent-child pairs with a 20-year or more difference in age at onset, 7 (35%) of the 20 children sampled did not have an APOE epsilon4 allele. CONCLUSIONS: Many LOAD families (approximately 25%) have at least 1 individual with EOAD, and in these individuals, the ratio of men to women is nearly 50%, suggesting a possible subtype of familial AD. The APOE genotype plays an important role in these early-onset cases, but at least one fourth of the risk must represent the influence of other genetic and/or environmental factors. These LOAD families with early-onset cases represent an important resource for investigation of these factors. SN - 0003-9942 UR - https://www.unboundmedicine.com/medline/citation/16966510/Early_onset_Alzheimer_disease_in_families_with_late_onset_Alzheimer_disease:_a_potential_important_subtype_of_familial_Alzheimer_disease_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/archneur.63.9.1307 DB - PRIME DP - Unbound Medicine ER -