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Title: Tau and Amyloid-β cerebrospinal fluid biomarkers have differential relationships with cognition in mild cognitive impairment
Austin Authors: Malpas, Charles B;Saling, Michael M ;Velakoulis, Dennis;Desmond, Patricia M;O’Brien, Terence J
Institutional Author: Alzheimer's Disease Neuroimaging Initiative
Affiliation: Melbourne Brain Centre, Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Victoria, Australia
Melbourne School of Psychological Sciences, the University of Melbourne, Melbourne, Victoria, Australia
Department of Neuropsychology, Austin Health, Heidelberg, Victoria, Australia
Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, Austin Health, Heidelberg, Victoria, Australia
Melbourne Neuropsychiatry Centre, Royal Melbourne Hospital, Victoria, Australia
Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia
Department of Radiology, University of Melbourne, Victoria, Australia
Department of Medical Imaging, Royal Melbourne Hospital, Parkville, Victoria, Australia
Department of Neurology, Royal Melbourne Hospital, Parkville, Victoria, Australia
Issue Date: 2015 2015-05-12
Publication information: Journal of Alzheimer's Disease 2015; 47(4): 965-975
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.
DOI: 10.3233/JAD-142643
Journal: Journal of Alzheimer's Disease
PubMed URL:
Type: Journal Article
Subjects: Amyloid-β
Cerebrospinal fluid
Mild cognitive impairment
Appears in Collections:Journal articles

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