Microglial alterations in human Alzheimer's disease following Aβ42 immunization

Abstract

Aims: In Alzheimer's disease (AD), microglial activation prompted by the presence of amyloid, has been proposed as an important contributor to the neurodegenerative process. Conversely following Aβ immunisation, phagocytic microglia have been implicated in plaque removal, potentially a beneficial effect. We have investigated the effects of Aβ42 immunisation on microglial activation and the relationship with Aβ42 load in human AD.

Methods: Immunostaining against Aβ42 and microglia (CD68 and HLA-DR) was performed in 9 immunised AD cases (iAD - AN1792, Elan Pharmaceuticals) and 8 unimmunised AD (cAD) cases.

Results: Although the Aβ42 load (% area stained of total area examined) was lower in the iAD than the cAD cases (p = 0.036), the CD68 load was higher (p = 0.046). In addition, in the iAD group, the CD68 level correlated with the Aβ42 load, consistent with the immunisation upregulating microglial phagocytosis when plaques are present. However, in 2 long-surviving iAD cases in whom plaques had been extensively cleared, the CD68 load was less than in controls. HLA-DR quantification did not show significant difference implying that the microglial activation may have related specifically to their phagocytic function. CD68 and HLA-DR loads in the pons were similar in both groups, suggesting that the differences in microglial activation in the cortex was due to the presence of AD pathology.

Conclusion: Our findings suggest that Aβ42 immunisation modifies the function of microglia by increasing their phagocytic activity and when plaques have been cleared, the level of phagocytosis is decreased below that seen in unimmunised AD.

More information

Identifiers

ORCID for Clive Holmes: orcid.org/0000-0003-1999-6912

ORCID for David Johnston: orcid.org/0000-0001-6703-6014

ORCID for James A.R. Nicoll: orcid.org/0000-0002-9444-7246

ORCID for Delphine Boche: orcid.org/0000-0002-5884-130X

Catalogue record

Export record

Altmetrics