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Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies
Published on: January 28, 2014
Biomarkers
Xiaqing Jiang1, Tina D Hoang2, Leslie M Shaw3
1University of California, San Francisco, San Francisco, CA, USA.
Insights
Alzheimer disease (AD) blood biomarkers like Aβ42/40, p-tau217, NfL, and GFAP are linked to cognitive function in midlife adults. Early AD pathology in midlife may impact cognitive decline, highlighting the importance of prevention strategies.
Area of Science:
- Neurology
- Biomarker Research
- Cognitive Science
Background:
- Limited research exists on Alzheimer disease (AD) blood biomarkers in midlife populations.
- Most studies focus on older adults, leaving a gap in understanding midlife cognitive associations.
Purpose of the Study:
- To investigate the relationship between plasma AD biomarkers and cognitive function in a midlife cohort.
- To explore associations between specific biomarkers (Aβ42/40, p-tau217, GFAP, NfL) and cognitive domains.
Main Methods:
- Cross-sectional study of 1,356 dementia-free participants (mean age 61).
- Assayed plasma Aβ42/40, p-tau217, GFAP, and NfL.
- Used linear regression to assess biomarker associations with cognitive performance and potential race interactions.
Main Results:
- Lower Aβ42/40 and higher p-tau217, NfL, and GFAP were associated with increased AD risk.
- Lower Aβ42/40, higher p-tau217, and higher p-tau217/Aβ42 correlated with worse processing speed and executive function.
- Higher NfL and GFAP were linked to deficits in multiple cognitive domains, independent of race.
Conclusions:
- Blood biomarkers suggest AD pathology and neurodegeneration may begin impacting midlife cognition.
- Midlife represents a critical window for AD prevention to potentially delay cognitive decline and dementia onset.
Background:
Despite a surge in studies on Alzheimer disease (AD) blood biomarkers, most evidence comes from clinical samples of older adults. The relationship between blood biomarkers and cognition in midlife remains poorly understood.
Method:
We cross-sectionally studied 1,356 dementia-free Black and White participants (58% women and 45% Black), enrolled in the Coronary Artery Risk Development in Young Adults Study (CARDIA) with a mean age of 61±3.6 (range 53-69) years. Five cognitive tests assessing different domains were administered. Plasma β-amyloid (Aβ) 42/40 and phosphorylated tau (p-tau)217 were assayed using the Fujirebio Lumipulse G1200 analyzer, while glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were analyzed using the Quanterix Simoa HD-X assay. Associations of demographic and clinical characteristics with plasma biomarker levels (log-transformed) were evaluated using linear regression. We also used linear regression to assess the standardized association between plasma biomarker level (per 1 SD) and midlife cognition, testing for effect modification by race.
Result:
Older age, White race, APOE ε4 carrier, and diabetes were associated with biomarker levels indicative of higher AD risk (lower Aβ42/40; higher p-tau217, p-tau217/Aβ42, NfL, and GFAP). After adjustment for age, sex, race, education, body mass index, and estimated glomerular filtration rate, lower Aβ42/40, higher p-tau217, and higher p-tau217/Aβ42 were each associated with worse performance on processing speed and executive function (Figure 1). Higher NfL was associated with worse performance on all five domains, while higher GFAP was associated with worse performance on processing speed and verbal fluency. These associations remained significant after additional adjustment for APOE and cardiovascular risk factors, with no clear pattern for race interaction in biomarker-cognition associations.
Conclusion:
AD pathology and neurodegeneration indicated by blood biomarkers may already start contributing to cognitive function in midlife. Young and middle adulthood is a critical time for AD prevention, which may delay the onset of cognitive decline and dementia among middle-aged and older adults.
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