ArticlePloS one2018
The nonlinear relationship between cerebrospinal fluid Aβ42 and tau in preclinical Alzheimer's disease.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- Longitudinal associations of rapid eye movement (REM) sleep and slow-wave sleep with plasma Alzheimer's disease biomarkers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Advances in biomarker discovery for canine cognitive dysfunction: a comprehensive structured narrative review and future perspectives.Veterinary research communications · 2026Review
- CSF fibrinogen predicts longitudinal Tau accumulation in cognitively unimpaired older adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Comparison of ERlangen Score with pTau/Aβ1-42 Ratio for Predicting Cognitive Decline and Conversion to Alzheimer's Disease.Brain sciences · 2025Article
- Heterogeneous Functional Regression for Subgroup Analysis.Journal of computational and graphical statistics : a joint publication of American Statistical Association, Institute of Mathematical Statistics, Interface Foundation of North America · 2024Article
- Elevated C-Reactive Protein in Older Men With Chronic Pain: Association With Plasma Amyloid Levels and Hippocampal Volume.The journals of gerontology. Series A, Biological sciences and medical sciences · 2024Article
- Article
- Longitudinal trajectories of Alzheimer's disease CSF biomarkers and blood pressure in cognitively healthy subjects.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Probable chronic pain, brain structure, and Alzheimer's plasma biomarkers in older men.The journal of pain · 2024Article
- Midlife cumulative deficit frailty predicts Alzheimer's disease-related plasma biomarkers in older adults.Age and ageing · 2024Article
- Alcohol Use Disorder and Dementia: A Review.Alcohol research : current reviews · 2024Review
- Cerebrospinal fluid proteomics in patients with Alzheimer's disease reveals five molecular subtypes with distinct genetic risk profiles.Nature aging · 2024Article
- Charting the Next Road Map for CSF Biomarkers in Alzheimer's Disease and Related Dementias.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- Genetic Risk for Alzheimer Disease and Plasma Tau Are Associated With Accelerated Parietal Cortex Thickness Change in Middle-Aged Adults.Neurology. Genetics · 2023Article
- Comparing Symmetric Dimethylarginine and Amyloid-β42 as Predictors of Alzheimer's Disease Development.Journal of Alzheimer's disease reports · 2023Article
- Integrated partially linear model for multi-center studies with heterogeneity and batch effect in covariates.Statistics · 2023Article
- Accelerated longitudinal changes and ordering of Alzheimer disease biomarkers across the adult lifespan.Brain : a journal of neurology · 2022Article
- Apolipoprotein E ɛ4-related effects on cognition are limited to the Alzheimer's disease spectrum.GeroScience · 2022Article
- Periodontal dysbiosis associates with reduced CSF Aβ42 in cognitively normal elderly.Alzheimer's & dementia (Amsterdam, Netherlands) · 2021Article
- Pathophysiological subtypes of Alzheimer's disease based on cerebrospinal fluid proteomics.Brain : a journal of neurology · 2020Article
Corrections and comments
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Authors and funding
17 authors.
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Abstract
Cerebrospinal fluid (CSF) studies consistently show that CSF levels of amyloid-beta 1-42 (Aβ42) are reduced and tau levels increased prior to the onset of cognitive decline related to Alzheimer's disease (AD). However, the preclinical prediction accuracy for low CSF Aβ42 levels, a surrogate for brain Aβ42 deposits, is not high. Moreover, the pathology data suggests a course initiated by tauopathy contradicting the contemporary clinical view of an Aβ initiated cascade. CSF Aβ42 and tau data from 3 normal aging cohorts (45-90 years) were combined to test both cross-sectional (n = 766) and longitudinal (n = 651) hypotheses: 1) that the relationship between CSF levels of Aβ42 and tau are not linear over the adult life-span; and 2) that non-linear models improve the prediction of cognitive decline. Supporting the hypotheses, the results showed that a u-shaped quadratic fit (Aβ2) best describes the relationship for CSF Aβ42 with CSF tau levels. Furthermore we found that the relationship between Aβ42 and tau changes with age-between 45 and 70 years there is a positive linear association, whereas between 71 and 90 years there is a negative linear association between Aβ42 and tau. The quadratic effect appears to be unique to Aβ42, as Aβ38 and Aβ40 showed only positive linear relationships with age and CSF tau. Importantly, we observed the prediction of cognitive decline was improved by considering both high and low levels of Aβ42. Overall, these data suggest an earlier preclinical stage than currently appreciated, marked by CSF elevations in tau and accompanied by either elevations or reductions in Aβ42. Future studies are needed to examine potential mechanisms such as failing CSF clearance as a common factor elevating CSF Aβxx analyte levels prior to Aβ42 deposition in brain.
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