Tau and Amyloid-β Cerebrospinal Fluid Biomarkers have Differential Relationships with Cognition in Mild Cognitive Impairment
Year: 2015
Type: article
Study design: Observational Study
Abstract: Alzheimer's disease (AD) is characterized by two primary pathologies: tau-related neurofibrillary tangles and the extracellular accumulation of amyloid-β (Aβ). The development of these pathologies is topologically distinct early in the disease, with Aβ beginning to accumulate as a diffuse, neocortical pathology, while tau-related pathology begins to form in mesial temporal regions. This study investigated the hypothesis that, by virtue of this distinction, there exist preferential associations between the primary pathologies and aspects of the cognitive phenotype. We investigated the relationship between cerebrospinal fluid (CSF) biomarkers for tau and Aβ pathologies with neurocognitive measures in 191 patients with mild cognitive impairment (MCI). Participants completed cognitive tests of new learning, information processing speed, and working memory. Separate regression models were computed and then followed up with mediation analyses to examine the predictive status of CSF biomarkers. The effect of Aβ on learning was mediated by phospho-tau (p = 0.008). In contrast, Aβ had a direct effect on information processing speed that was not mediated by phospho-tau (p = 0.59). No predictors were significant for working memory. This study provided evidence for a differential relationship of Aβ and phospho-tau pathologies on the neurocognitive phenotype of MCI. This supports the proposition that these primary AD pathologies maximally affect different aspects of cognition, and has potential implications for cognitive assessments and the use of biomarkers in disease-modifyingtherapeutic trials.
Source: Journal of Alzheimer s Disease
DOI: 10.3233/jad-142643
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: U.S. Department of Defense, Alzheimer's Association, Bristol-Myers Squibb, Eli Lilly and Company, International Business Machines Corporation, Pfizer, Biogen, University of Southern California, Medpace, Meso Scale Diagnostics, Synarc, Alzheimer's Disease Neuroimaging Initiative, BioClinica, Novartis Pharmaceuticals Corporation, Eisai, Servier, IXICO, National Institutes of Health, Genentech, University of California, San Diego, Canadian Institutes of Health Research, National Institute on Aging, National Institute of Biomedical Imaging and Bioengineering, Johnson and Johnson Pharmaceutical Research and Development, Janssen Alzheimer Immunotherapy Research And Development
Awards: G104586243, G1120803110, G29951154, G3553156159, G3752451908, G3870774570, G4501223628, G5209990037, G5654639750, Alzheimer's Disease Neuroimaging Initiative, G5740349702, G6371410416, G6899163935, Boston University Alzheimer's Disease Center, G781725486, G839208290, G8895907669, G9000122335, Alzheimer's Disease Neuroimaging Initiative (ADNI4)
OpenAlex ID: W2108479773