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Cited by 77Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchAmyotrophic Lateral Sclerosis Research

Early-Onset Alzheimer Disease in Families With Late-Onset Alzheimer Disease: A Potential Important Subtype of Familial Alzheimer Disease

Brickell, Kiri L., Steinbart, Ellen J., Rumbaugh, Malia, Payami, Haydeh, Schellenberg, Gerard D., Van Deerlin, Vivianna, Yuan, Wuxing, Bird, Thomas D.·2006·Archives of Neurology
DOI 10.1001/archneur.63.9.1307
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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.

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  • Autosomal dominant Alzheimer's disease (ADAD) is very rare, accounting for less than 1% of all cases of Alzheimer's disease.

    “ADAD is very rare, accounting for less than <1% of all cases of AD [2, 31–33]”

    From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [32]

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Authors
Brickell, K. L., Steinbart, E. J., Rumbaugh, M., Payami, H., Schellenberg, G. D., Van Deerlin, V., Yuan, W., & Bird, T. D.
Affiliations
  • University of Washington (US)
  • Wadsworth Center (US)
  • University of Pennsylvania (US)
  • VA Puget Sound Health Care System (US)
ORCID
Venue
Archives of Neurology
Publisher
American Medical Association (AMA)
Published
2006-09-01
Volume
63
Issue
9
Pages
1307
ISSN
0003-9942 (ISSN-L)
DOI
10.1001/archneur.63.9.1307
OpenAlex
W2110374568
Cited by
77
References
21
Citations by year
2026: 1 · 2024: 5 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 10 · 2019: 5 · 2018: 2 · 2017: 4 · 2016: 4 · 2015: 1 · 2014: 7 · 2013: 6 · 2012: 7
FWCI
1.99
Type
journal article
Language
en
Open access
closed
Locations
  • Archives of Neurology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Veterans Affairs
  • Alzheimer's Association
  • University of Southern California
  • University of Minnesota
  • Neurological Foundation of New Zealand
  • National Institutes of Health
  • Geriatric Research Education and Clinical Center
  • National Institute on Aging (P30AG008017, P50AG005136)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
Keywords
early-onset Alzheimer's disease, late-onset Alzheimer's disease, familial Alzheimer's disease, apolipoprotein E, APOE ε4, genetic risk factors, age of onset, parent-child dyads, kindred, sex differences
MeSH terms
Aged, Aged, 80 and over, Alleles, Alzheimer Disease, Apolipoproteins E, Family Health, Female, Gene Frequency, Humans, Male, Middle Aged, Neuropsychological Tests, Risk Factors, Age of Onset, Genetic Predisposition to Disease

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