Role of Family History for Alzheimer Biomarker Abnormalities in the Adult Children Study
Open accessAbstract
OBJECTIVE: To assess whether family history (FH) of Alzheimer disease (AD) alone influences AD biomarker abnormalities. DESIGN: Adult Children Study. SETTING: Washington University's Charles F. and Joanne Knight Alzheimer's Disease Research Center. PARTICIPANTS: A total of 269 cognitively normal middle- to older-aged individuals with and without an FH for AD. MAIN OUTCOME MEASURES: Clinical and cognitive measures, magnetic resonance imaging-based brain volumes, diffusion tensor imaging-based white matter microstructure, cerebrospinal fluid biomarkers, and molecular imaging of cerebral fibrillar amyloid with positron emission tomography using the [(11)C] benzothiazole tracer, Pittsburgh compound B. RESULTS: A positive FH for AD was associated with an age-related decrease of cerebrospinal fluid Aβ42; the ε4 allele of apolipoprotein E (APOE4) did not alter this effect. Age-adjusted cerebrospinal fluid Aβ42 was decreased for individuals with APOE4 compared with the level for those without, and the decrease was larger for individuals with a positive FH compared with the decrease for those without. The variation of cerebrospinal fluid tau and Pittsburgh compound B mean cortical binding potential increased by age. For individuals younger than 55, an age-related increase in mean cortical binding potential was associated with APOE4 but not FH. For individuals older than 55, a positive FH and a positive APOE4 implied the fastest age-related increase in mean cortical binding potential. A positive FH was associated with decreased fractional anisotropy from diffusion tensor imaging in the genu and splenium of the corpus callosum. CONCLUSION: Independent of APOE4, FH is associated with age-related change of several cerebrospinal fluid, Pittsburgh compound B, and diffusion tensor imaging biomarkers in cognitively normal middle- to older-aged individuals, suggesting that non- APOE susceptibility genes for AD influence AD biomarkers.
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The APOE ε4 allele has been linked to increased risk for Alzheimer's disease while the ε2 allele may provide protection from Alzheimer's disease.
“The APOE ε 4 allele of apolipoprotein E gene (APOE ε 4) has been linked to increased risk for Alzheimer's disease 19 while the ε 2 allele (APOE ε 2) may provide protection from Alzheimer's disease 20,21 .”
From OASIS-3: Longitudinal Neuroimaging, Clinical, and Cognitive Dataset for Normal Aging and Alzheimer Disease (2019) · cites this paper as [19]
The Methods (Statistical Analysis; page unavailable) treat APOE ε4 as a risk factor, and the Results associate it with Alzheimer-related biomarker abnormalities. The paper does not address whether APOE ε2 protects against Alzheimer's disease, so that part of the claim is unsupported. (LLM, conf=0.85)
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- Authors
- Xiong, C.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Xiong, Chengjie
- ORCID
- Xiong, Chengjie
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2011-10-01
- Volume
- 68
- Issue
- 10
- Pages
- 1313
- ISSN
- 0003-9942 (ISSN-L)
- PMC
- PMC3327304
- OpenAlex
- W2134795091
- Cited by
- 56
- References
- 59
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 5 · 2022: 2 · 2021: 2 · 2019: 5 · 2018: 1 · 2017: 3 · 2016: 4 · 2015: 3 · 2014: 9 · 2013: 9 · 2012: 9
- FWCI
- 5.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (P 50 AG05681, P50AG005681, P01AG026276)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Keywords
- Alzheimer's disease, family history (medicine), Alzheimer's disease biomarkers, cerebrospinal fluid amyloid-beta 42, APOE ε4, Pittsburgh compound B, cerebral amyloid deposition, tau protein, white matter microstructure, corpus callosum, age-related changes, cognitively normal older adults, genetic susceptibility
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alzheimer Disease, Aniline Compounds, Attention, Brain, Carbon Radioisotopes, Cognition Disorders, Family Health, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Peptide Fragments, Psychiatric Status Rating Scales, Reaction Time, Residence Characteristics, Statistics as Topic, Thiazoles, Cohort Studies, Biomarkers, Amyloid beta-Peptides, Disease Progression, Positron-Emission Tomography, Apolipoprotein E4
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