High cerebrospinal amyloid-β 42 is associated with normal cognition in individuals with brain amyloidosis

Authors

Andrea Sturchio, James J. and Joan A. Gardner Family Center for Parkinson's disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.
Alok K. Dwivedi, Division of Biostatistics & Epidemiology, Department of Molecular and Translational Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
Christina B. Young, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Tarja Malm, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Luca Marsili, James J. and Joan A. Gardner Family Center for Parkinson's disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.
Jennifer S. Sharma, James J. and Joan A. Gardner Family Center for Parkinson's disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.
Abhimanyu Mahajan, James J. and Joan A. Gardner Family Center for Parkinson's disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.
Emily J. Hill, James J. and Joan A. Gardner Family Center for Parkinson's disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.
Samir El Andaloussi, Department of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, Stockholm, Sweden.
Kathleen L. Poston, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Fredric P. Manfredsson, Department of Neurobiology, Barrow Neurological Institute, Phoenix, AZ, USA.Follow
Lon S. Schneider, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
Kariem Ezzat, Department of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, Stockholm, Sweden.
Alberto J. Espay, James J. and Joan A. Gardner Family Center for Parkinson's disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.

Document Type

Article

Abstract

Background: Brain amyloidosis does not invariably predict dementia. We hypothesized that high soluble 42-amino acid β amyloid (Aβ42) peptide levels are associated with normal cognition and hippocampal volume despite increasing brain amyloidosis. Methods: This cross-sectional study of 598 amyloid-positive participants in the Alzheimer's Disease Neuroimaging Initiative cohort examined whether levels of soluble Aβ42 are higher in amyloid-positive normal cognition (NC) individuals compared to mild cognitive impairment (MCI) and Alzheimer's disease (AD) and whether this relationship applies to neuropsychological assessments and hippocampal volume measured within the same year. All subjects were evaluated between June 2010 and February 2019. Brain amyloid positivity was defined as positron emission tomography-based standard uptake value ratio (SUVR) ≥1.08 for F-florbetaben or 1.11 for F-florbetapir, with higher SUVR indicating more brain amyloidosis. Analyses were adjusted for age, sex, education, -tau, -tau, and centiloids levels. Findings: Higher soluble Aβ42 levels were observed in NC (864.00 pg/ml) than in MCI (768.60 pg/ml) or AD (617.46 pg/ml), with the relationship between NC, MCI, and AD maintained across all amyloid tertiles. In adjusted analysis, there was a larger absolute effect size of soluble Aβ42 than SUVR for NC (0.82 vs. 0.40) and MCI (0.60 vs. 0.26) versus AD. Each standard deviation increase in Aβ42 was associated with greater odds of NC than AD (adjusted odds ratio, 6.26; < 0.001) or MCI (1.42; = 0.006). Higher soluble Aβ42 levels were also associated with better neuropsychological function and larger hippocampal volume. Interpretation: Normal cognition and hippocampal volume are associated with preservation of high soluble Aβ42 levels despite increasing brain amyloidosis. Funding: Please refer to the Funding section at the end of the article.

Keywords

Alzheimer's disease, Atrophy, Hippocampus, Β-amyloid

Publication Date

8-1-2021

Publication Title

EClinicalMedicine

E-ISSN

2589-5370

Volume

38

First Page

100988

PubMed ID

34505023

Digital Object Identifier (DOI)

10.1016/j.eclinm.2021.100988

Recommended Citation

Sturchio, Andrea; Dwivedi, Alok K.; Young, Christina B.; Malm, Tarja; Marsili, Luca; Sharma, Jennifer S.; Mahajan, Abhimanyu; Hill, Emily J.; Andaloussi, Samir El; Poston, Kathleen L.; Manfredsson, Fredric P.; Schneider, Lon S.; Ezzat, Kariem; and Espay, Alberto J., "High cerebrospinal amyloid-β 42 is associated with normal cognition in individuals with brain amyloidosis" (2021). Translational Neuroscience. 1424.
https://scholar.barrowneuro.org/neurobiology/1424