Article ; Online: Anti-Correlated Cerebrospinal Fluid Biomarker Trajectories in Preclinical Alzheimer's Disease.
Journal of Alzheimer's disease : JAD
2016 Volume 51, Issue 4, Page(s) 1085–1097
Abstract: Background: The earliest stage of preclinical Alzheimer's disease (AD) is defined by low levels of cerebrospinal fluid (CSF) amyloid-β (Aβ42). However, covariance in longitudinal dynamic change of Aβ42 and tau in incipient preclinical AD is poorly ... ...
| Abstract | Background: The earliest stage of preclinical Alzheimer's disease (AD) is defined by low levels of cerebrospinal fluid (CSF) amyloid-β (Aβ42). However, covariance in longitudinal dynamic change of Aβ42 and tau in incipient preclinical AD is poorly understood. Objective: To examine dynamic interrelationships between Aβ42 and tau in preclinical AD. Methods: We followed 47 cognitively intact participants (CI) with available CSF data over four years in ADNI. Based on longitudinal Aβ42 levels in CSF, CI were classified into three groups: 1) Aβ42 stable with normal levels of Aβ42 over time (n = 15); 2) Aβ42 declining with normal Aβ42 levels at baseline but showing decline over time (n = 14); and 3) Aβ42 levels consistently abnormal (n = 18). Results: In the Aβ42 declining group, suggestive of incipient preclinical AD, CSF phosphorylated tau (p-tau) showed a similar longitudinal pattern of increasing abnormality over time (p = 0.0001). Correlation between longitudinal slopes of Aβ42 and p-tau confirmed that both trajectories were anti-correlated (rho = -0.60; p = 0.02). Regression analysis showed that Aβ42 slope (decreasing Aβ42) predicted p-tau slope (increasing p-tau) (R2 = 0.47, p = 0.03). Atrophy in the hippocampus was predicted by the interaction of Aβ42 and p-tau slopes (p < 0.0001) only in this incipient preclinical AD group. In all groups combined, memory decline was predicted by p-tau. Conclusions: The evolution of Aβ42 and p-tau CSF biomarkers in CI subjects follows an anti-correlated trajectory, i.e., as Aβ42 declined, p-tau increased, and thus was suggestive of strong temporal coincidence. Rapid pathogenic cross-talk between Aβ42 and p-tau thus may be evident in very early stages of preclinical AD. |
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| MeSH term(s) | Adult ; Aged ; Aged, 80 and over ; Alzheimer Disease/cerebrospinal fluid ; Alzheimer Disease/diagnosis ; Amyloid beta-Peptides/cerebrospinal fluid ; Atrophy ; Brain/diagnostic imaging ; Brain/pathology ; Disease Progression ; Female ; Humans ; Longitudinal Studies ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neuropsychological Tests ; Peptide Fragments/cerebrospinal fluid ; Prodromal Symptoms ; Regression Analysis ; Statistics, Nonparametric ; tau Proteins/cerebrospinal fluid |
| Chemical Substances | Amyloid beta-Peptides ; Peptide Fragments ; amyloid beta-protein (1-42) ; tau Proteins |
| Language | English |
| Publishing date | 2016-02-29 |
| Publishing country | Netherlands |
| Document type | Journal Article ; Research Support, N.I.H., Extramural |
| ZDB-ID | 1440127-7 |
| ISSN | 1875-8908 ; 1387-2877 |
| ISSN (online) | 1875-8908 |
| ISSN | 1387-2877 |
| DOI | 10.3233/JAD-150937 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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