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Longitudinal relationships among biomarkers for Alzheimer disease in the Adult Children Study
Open accessAbstract
OBJECTIVE: To determine whether and how longitudinal rates of change in MRI volumetrics, CSF concentrations of Alzheimer-related proteins, molecular imaging of cerebral fibrillar amyloid with PET using the [(11)C] benzothiazole tracer, Pittsburgh compound B (PiB), and cognition were associated among asymptomatic middle-aged to older individuals. METHODS: Multivariate mixed models for repeated measures were used to assess the correlations on the rates of changes across markers. RESULTS: Among 209 asymptomatic middle-aged to older individuals longitudinally followed for up to 11 years (mean 6.7 years), a faster intraindividual decrease in CSF Aβ42 was associated with a faster increase in PiB mean cortical standardized uptake value ratio (MCSUVR, p = 0.04), but not others. The rate of change in CSF tau (and Ptau181) was correlated with the rate of change in PiB MCSUVR (p = 0.002), hippocampal volume (p = 0.04), and global cognition (p = 0.008). The rate of change in hippocampal volume was correlated with the rate of change in global cognition (p = 0.04). Only 3 significant correlations were observed at baseline: CSF Aβ42 and PiB MCSUVR (p < 0.001), CSF tau and PiB MCSUVR (p < 0.001), and CSF Aβ42 and global cognition (p = 0.01). CONCLUSIONS: CSF tau (Ptau181), PiB MCSUVR, and hippocampal volume were all longitudinally correlated with each other, whereas CSF Aβ42 was correlated only with PiB binding. Unlike the baseline values, the longitudinal change in CSF tau (Ptau181) and hippocampal volume were correlated with the longitudinal change in global cognition, validating the role of these biomarkers in Alzheimer disease prevention trials.
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“Consequently, a widely held view is that amyloid biomarkers represent the earliest evidence of AD neuropathologic change currently detectable in living persons [9,11,72,103,104].”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [104]
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“Compared with the simple correlation estimation method (Pearson or Spearman correlation), the multivariate LME model can adjust for covariates such as EYO, as well as accounting for the correlation within the family cluster63,64.”
From A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease (2020) · cites this paper as [64]
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Metadata
- Authors
- Xiong, C., Jasielec, M. S., Weng, H., Fagan, A. M., Benzinger, T. L. S., Head, D., Hassenstab, J., Grant, E., Sutphen, C. L., Buckles, V., Moulder, K. L., & Morris, J. C.
- Affiliations
- From the Charles F. and Joanne Knight Alzheimer's Disease Research Center (C.X., M.S.J., H.W., A.M.F., T.L.S.B., D.H., J.H., E.G., C.L.S., V.B., K.L.M., J.C.M.), Departments of Neurology (V.B., K.L.M., A.M.F., J.H., J.C.M., C.L.S.), Pathology and Immunology (J.C.M.), Physical Therapy (J.C.M.), and Occupational Therapy (J.C.M.), Division of Biostatistics (C.X., M.S.J., H.W., E.G.), and Departments of Psychology (D.H., J.H.), Radiology (T.L.S.B., D.H.), and Neurological Surgery (T.L.S.B.), Washington...
- ORCID
- Venue
- Neurology
- Published
- 2016-04-19
- Volume
- 86
- Issue
- 16
- Pages
- 1499-1506
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC4836885
- OpenAlex
- W2308877313
- Cited by
- 54
- References
- 39
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 3 · 2023: 8 · 2022: 4 · 2021: 3 · 2020: 11 · 2019: 10 · 2018: 3 · 2016: 1
- FWCI
- 4.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG034119, P50AG005681, P01AG003991, P01AG026276)
- National Institute of Diabetes and Digestive and Kidney Diseases (K23DK094982)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Oncology › Cancer-related cognitive impairment studies
- Keywords
- Alzheimer's disease, biomarkers, CSF tau, CSF amyloid-beta 42, Pittsburgh compound B, amyloid PET, hippocampal volume, longitudinal change, cognition, biomarker correlation
- MeSH terms
- Adult, Aged, Alzheimer Disease, Apolipoproteins E, Brain, Cognition, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Middle Aged, Organ Size, Peptide Fragments, Phosphorylation, Biomarkers, Amyloid beta-Peptides, tau Proteins, Adult Children, Positron-Emission Tomography
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