Abstract
BackgroundApolipoprotein E4 (APOE4) and ageing are the most important known risk factors for late-onset Alzheimer’s disease (AD). In the present study, we determined the alterations of IgG, CD19, and Aβ in various brain regions of uninfected male and female APOE3- and APOE4-TR mice at the age of 3 and 10 months to elucidate impacts of AD risk factors on alterations of brain IgG.ResultsPositive staining for IgG was distributed across the brain, including neocortex, entorhinal cortex, hippocampus, thalamus and cerebellum. IgG positive staining was mainly located on microglia, but not astrocytes. Some IgG positive neurons were also observed, but only in mediodorsal thalamic nucleus. Compared with APOE3-TR mice, 10-month-old female APOE4-TR mice had lower IgG level in AD susceptible brain regions such as neocortex, entorhinal cortex and hippocampus, but no significant changes in thalamus and cerebellum, two regions nearly intact in AD. In addition, the expression of CD19, a specific marker for mature B cells, was significantly reduced in the hippocampus of 10-month-old female APOE4-TR mice. Although there were no obvious differences in plasma IgG levels between APOE4- and age matched female APOE3-TR mice, significant decreased B cell amount in blood of 10-month-old female APOE4-TR mice have also been found. Moreover, more obvious positive staining for Aβ was observed in the cortex of 10-month-old female APOE4-TR mice than other groups.ConclusionsOur study demonstrated that AD risk factors were associated with IgG alterations in various brain regions, which might result from the defects of humoral immunity and lead to the impairment of IgG-mediated clearance of Aβ by microglia, therefore facilitated AD progression.
Highlights
Apolipoprotein E4 (APOE4) and ageing are the most important known risk factors for late-onset Alzheimer’s disease (AD)
The aim of our study was to determine whether APOE4, ageing will cause an alteration of Immunoglobulin G (IgG) level and distribution in specific brain regions of the transgenic mice where are the differences come from
The blood cells were incubated with 500 μl (1:500 diluted in flow staining buffer) rat anti-mouse CD19-FITC (BioLegend) for 30 min at room temperature (RT) in the dark, and 2 ml 1× RBC Lysis Buffer was added for 8 min at RT in the dark
Summary
Apolipoprotein E4 (APOE4) and ageing are the most important known risk factors for late-onset Alzheimer’s disease (AD). Alzheimer’s disease (AD) is the major age-related neurodegenerative disease, which is characterized by the accumulation of β-amyloid (Aβ) plaques and tau-laden neurofibrillary tangles [1,2,3]. It is still unsettled what causes Alzheimer’s disease. Certain factors like apolipoprotein E4 (APOE4) and ageing increase the risk of developing this incurable disease. APOE4 coupled with aging significantly increases AD risk. Studies showed that APOE4 confers greater risk of AD for women than men, with worse cognition deficits and neuropathology of plaques and tangles [5]
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