Background Naturally occurring autoantibodies against amyloid β (Aβ) peptide exist in the serum and cerebrospinal fluid (CSF) of healthy individuals. Recently, it was reported that administration of intravenous immunoglobulin at the mild cognitive impairment (MCI) stage of Alzheimer's disease (AD) reduces brain atrophy.
Objective To examine the association between naturally occurring anti-Aβ autoantibodies and brain atrophy in patients with cognitive impairment.
Methods Serum and CSF levels of anti-Aβ autoantibodies and CSF biomarkers were evaluated in 68 patients with cognitive impairment, comprising 44 patients with AD, 19 patients with amnestic MCI and five patients with non-Alzheimer's dementia. The degree of brain atrophy was assessed using the voxel-based specific regional analysis system for AD, which targets the volume of interest (VOI) in medial temporal structures, including the whole hippocampus, entorhinal cortex and amygdala.
Results CSF levels of anti-Aβ autoantibodies were inversely correlated with the extent and severity of VOI atrophy, and the ratio of VOI/grey matter atrophy in patients with AD, but not in MCI or non-AD patients. Serum levels of anti-Aβ autoantibodies were not associated with these parameters in any of the patient groups.
Conclusions These results indicate that CSF levels of naturally occurring anti-Aβ autoantibodies are inversely associated with the degree of the VOI atrophy in patients with AD. Although the mechanism is unclear, CSF levels of naturally occurring anti-Aβ autoantibodies may be implicated in the progression of atrophy of the whole hippocampus, entorhinal cortex and amygdala, in AD.
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Contributors AK was involved in the study design, data collection, data analysis, statistical analysis and drafting of the manuscript. MT and KS was involved in the data analysis and drafting of the manuscript. NY and YH was involved in the data collection and drafting of the manuscript. TI was involved in the study design and drafting of the manuscript.
Funding Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science (grant number 26461290).
Competing interests None declared.
Patient consent Obtained.
Ethics approval Institutional Review Board of Gifu University Graduate School of Medicine.
Provenance and peer review Not commissioned; externally peer reviewed.