Abstract
Physiological β-amyloid autoantibodies (Aβ-autoantibodies) are currently investigated as potential diagnostic and therapeutic tools for Alzheimer’s disease (AD). In previous studies, their determination in serum and cerebrospinal fluid (CSF) using indirect ELISA has provided controversial results, which may be due to the presence of preformed Aβ antigen-antibody immune complexes. Based on the epitope specificity of the Aβ-autoantibodies, recently elucidated in our laboratory, we developed (a) a sandwich ELISA for the determination of circulating Aβ-IgG immune complexes and (b) an indirect ELISA for the determination of free Aβ-autoantibodies. This methodology was applied to the analysis of serum samples from healthy individuals within the age range of 18 to 89 years. Neuropsychological examination of the participants in this study indicated non-pathological, age-related cognitive decline, revealed especially by tests of visual memory and executive function, as well as speed-related tasks. The ELISA serum determinations showed significantly higher levels of Aβ-IgG immune complexes compared to free Aβ-autoantibodies, while no correlation with age or cognitive performance of the participants was found.
Highlights
IntroductionA modest decline of fluid cognitive abilities (e.g., psychomotor speed, attention, short-term storage, verbal and visual episodic memory, visuospatial abilities and verbal fluency) can be observed, while crystallized cognitive functions such as semantic and procedural knowledge remain unimpaired [1,2,3]
During healthy aging, a modest decline of fluid cognitive abilities can be observed, while crystallized cognitive functions such as semantic and procedural knowledge remain unimpaired [1,2,3]
Physiological b-amyloid autoantibodies (Ab-autoantibodies) have been identified in serum and cerebrospinal fluid (CSF) of healthy individuals and Alzheimer’s disease (AD) patients, as well as in human intravenous immunoglobulin preparations (IVIg), which are fractionated blood products used for the treatment of immune deficiencies and other disorders [9]
Summary
A modest decline of fluid cognitive abilities (e.g., psychomotor speed, attention, short-term storage, verbal and visual episodic memory, visuospatial abilities and verbal fluency) can be observed, while crystallized cognitive functions such as semantic and procedural knowledge remain unimpaired [1,2,3]. Healthy aging is further associated with biological changes, among which a decline in the specific immune response to antigenic stimuli was reported [6]. Considering that IVIg preparations contain Ab-autoantibodies, they were used in small pilot trials for the treatment of AD patients [12,13] and have been introduced into clinical trials as a potential AD treatment (www.clinicaltrials.gov; [12]).
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