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Alzheimers Dement. 2018 Jul;14(7):869-879. doi: 10.1016/j.jalz.2018.01.012. Epub 2018 Mar 23.

Longitudinal decreases in multiple cerebrospinal fluid biomarkers of neuronal injury in symptomatic late onset Alzheimer's disease.

Author information

1
Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA; Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA.
2
Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA.
3
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
4
Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA; Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA.
5
Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA; Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: fagana@wustl.edu.

Abstract

INTRODUCTION:

Individuals in early stages of Alzheimer's disease are a targeted population for secondary prevention trials aimed at preserving normal cognition. Understanding within-person biomarker(s) change over time is critical for trial enrollment and design.

METHODS:

Longitudinal cerebrospinal fluid samples from the Alzheimer's Disease Neuroimaging Initiative were assayed for novel markers of neuronal/synaptic injury (visinin-like protein 1, Ng, and SNAP-25) and neuroinflammation (YKL-40) and compared with β amyloid 42, tau, and phospho-tau181. General linear mixed models were used to compare within-person rates of change in three clinical groups (cognitively normal, mild cognitive impairment, and Alzheimer's disease) further defined by β amyloid status.

RESULTS:

Levels of injury markers were highly positively correlated. Despite elevated baseline levels as a function of clinical status and amyloid-positivity, within-person decreases in these measures were observed in the early symptomatic, amyloid-positive Alzheimer's disease group.

DISCUSSION:

Knowledge of within-person biomarker change will impact interpretation of biomarker outcomes in clinical trials that are dependent on disease stage.

KEYWORDS:

Cerebrospinal fluid; Longitudinal biomarkers; Neuronal injury

PMID:
29580670
PMCID:
PMC6110083
[Available on 2019-07-01]
DOI:
10.1016/j.jalz.2018.01.012
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