Tau and Amyloid-β Cerebrospinal Fluid Biomarkers have Differential Relationships with Cognition in Mild Cognitive Impairment

Charles B Malpas; Michael M Saling; Dennis Velakoulis; Patricia Desmond; Terence J O'Brien; Alzheimer’s Disease Neuroimaging Initiative

doi:10.3233/JAD-142643

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Tau and Amyloid-β Cerebrospinal Fluid Biomarkers have Differential Relationships with Cognition in Mild Cognitive Impairment

Journal article

Peer reviewed

Tau and Amyloid-β Cerebrospinal Fluid Biomarkers have Differential Relationships with Cognition in Mild Cognitive Impairment

Charles B Malpas, Michael M Saling, Dennis Velakoulis, Patricia Desmond, Terence J O'Brien and Alzheimer’s Disease Neuroimaging Initiative

Journal of Alzheimer's disease, Vol.47(4), pp.965-975

2015

DOI: 10.3233/JAD-142643

PMCID: PMC6287609

PMID: 26401775

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https://www.ncbi.nlm.nih.gov/pmc/articles/6287609View

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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.

Phosphorylation

Peptide Fragments - cerebrospinal fluid

Humans

Middle Aged

Male

tau Proteins - cerebrospinal fluid

Cognitive Dysfunction - cerebrospinal fluid

Neuropsychological Tests

Learning - physiology

Regression Analysis

Aged, 80 and over

Amyloid beta-Peptides - cerebrospinal fluid

Cognition - physiology

Cognitive Dysfunction - psychology

Female

Aged

Biomarkers - cerebrospinal fluid

Databases, Factual

Details

Title: Subtitle: Tau and Amyloid-β Cerebrospinal Fluid Biomarkers have Differential Relationships with Cognition in Mild Cognitive Impairment
Creators: Charles B Malpas - Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Australia
Michael M Saling - Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, Austin Hospital, Australia
Dennis Velakoulis - Department of Psychiatry, University of Melbourne, Melbourne, Australia
Patricia Desmond - Department of Medical Imaging, Royal Melbourne Hospital, Victoria, Australia
Terence J O'Brien - Department of Neurology, Royal Melbourne Hospital, Victoria, Australia
Alzheimer’s Disease Neuroimaging Initiative
Contributors: Laura L Boles-Ponto (Contributor) - University of Iowa, Radiology
Resource Type: Journal article
Publication Details: Journal of Alzheimer's disease, Vol.47(4), pp.965-975
DOI: 10.3233/JAD-142643
PMID: 26401775
PMCID: PMC6287609
NLM abbreviation: J Alzheimers Dis
ISSN: 1387-2877
eISSN: 1875-8908
Publisher: Netherlands
Grant note: U01 AG024904 / NIA NIH HHS P30 AG013846 / NIA NIH HHS U19 AG024904 / NIA NIH HHS
Language: English
Date published: 2015
Academic Unit: Radiology; Pharmaceutical Sciences and Experimental Therapeutics
Record Identifier: 9984051775102771

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19 Times Cited - Web of Science