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Research paper
Association between naturally occurring anti-amyloid β autoantibodies and medial temporal lobe atrophy in Alzheimer's disease
  1. Akio Kimura1,
  2. Masao Takemura2,3,
  3. Kuniaki Saito4,
  4. Nobuaki Yoshikura1,
  5. Yuichi Hayashi1,
  6. Takashi Inuzuka1
  1. 1Department of Neurology and Geriatrics, Gifu University Graduate School of Medicine, Gifu, Japan
  2. 2Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
  3. 3Advanced Diagnostic System Research Laboratory, Fujita Health University Graduate School of Health Sciences, Toyoake, Aichi, Japan
  4. 4Department of Disease Control and Prevention, Fujita Health University Graduate School of Health Sciences, Toyoake, Aichi, Japan
  1. Correspondence to Dr Akio Kimura, Department of Neurology and Geriatrics, Gifu University Graduate School of Medicine, Gifu, 1-1 Yanagido, Gifu 501-1194, Japan; kimura1{at}gifu-u.ac.jp

Abstract

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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