Title | Anti-Correlated Cerebrospinal Fluid Biomarker Trajectories in Preclinical Alzheimer's Disease. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Gomar, JJ, Conejero-Goldberg, C, Davies, P, Goldberg, TE |
Corporate Authors | Alzheimer’s Disease Neuroimaging Initiative |
Journal | J Alzheimers Dis |
Volume | 51 |
Issue | 4 |
Pagination | 1085-97 |
Date Published | 2016 |
ISSN | 1875-8908 |
Keywords | Adult, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Atrophy, Brain, Disease Progression, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Peptide Fragments, Prodromal Symptoms, Regression Analysis, Statistics, Nonparametric, tau Proteins |
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 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. |
DOI | 10.3233/JAD-150937 |
Alternate Journal | J. Alzheimers Dis. |
PubMed ID | 26967213 |
Grant List | R01 AG038734 / AG / NIA NIH HHS / United States |