Neuroinflammation in Alzheimer's disease wanes with age

Abstract

Background: Inflammation is a prominent feature in Alzheimer's disease (AD). It has been proposed that aging has an effect on the function of inflammation in the brain, thereby contributing to the development of age-related diseases like AD. However, the age-dependent relationship between inflammation and clinical phenotype of AD has never been investigated.

Methods: In this study we have analysed features of the neuroinflammatory response in clinically and pathologically confirmed AD and control cases in relation to age (range 52-97 years). The mid-temporal cortex of 19 controls and 19 AD cases was assessed for the occurrence of microglia and astrocytes by immunohistochemistry using antibodies directed against CD68 (KP1), HLA class II (CR3/43) and glial fibrillary acidic protein (GFAP).

Results: By measuring the area density of immunoreactivity we found significantly more microglia and astrocytes in AD cases younger than 80 years compared to older AD patients. In addition, the presence of KP1, CR3/43 and GFAP decreases significantly with increasing age in AD.

Conclusion: Our data suggest that the association between neuroinflammation and AD is stronger in relatively young patients than in the oldest patients. This age-dependent relationship between inflammation and clinical phenotype of AD has implications for the interpretation of biomarkers and treatment of the disease.

Figure 1

Relative occurrence of pathological hallmarks and neuroinflammation in controls and AD cases. Data represent the occurrence (Y axis in number per 2 mm²) of Aβ immunoreactive plaques, AT8 immunoreactive plaques and tangles, and the relative occurrence (Y axis in percentage) of quantified KP1 (CD68), CR3/43 (HLA class II), and GFAP immunoreactivity in control (CTRL) and AD cases of 80 years and younger (≤ 80) or older than 80 years (> 80). Data are shown as mean level ± S.E.M.. * indicates significant difference.

Figure 2

Neuroinflammation in relation to age in controls and AD cases. Data represent the relation between age (X axis, in years) and quantified KP1 (CD68), CR3/43 (HLA class II), and GFAP immunoreactivity (Y axis, in arbitrary units) for controls (open dots) and AD patients (closed dots). Straight lines represent regression lines, with corresponding 95% confidence intervals.