Abstract
BackgroundAlzheimer’s disease (AD) is characterized by the pathological deposition of amyloid-β (Aβ) protein-containing plaques. Microglia and astrocytes are commonly attracted to the plaques by an unknown mechanism that may involve cell adhesion. One cell adhesion family of proteins, the cadherins, are widely expressed in the central nervous system. Therefore, our study was designed to map the expression of cadherins in AD mouse brains. A particular focus was on plaques because diverse mRNA-species were found in plaques and their surrounding area in brains of AD patients.MethodsIn this study, we used in situ hybridization to visualize cadherin expression in brains of two mouse models for AD (APP/PS1 and APP23).ResultsA variable number of plaques was detected in transgenic brain sections, depending on the probe used. Our first impression was that the cadherin probes visualized specific mRNA expression in plaques and that endogenous staining was unaffected. However, control experiments revealed unspecific binding with sense probes. Further experiments with variations in probe length, probe sequence, molecular tag and experimental procedure lead us to conclude that cRNA probes bind generally and in an unspecific manner to plaques.ConclusionsWe demonstrate unspecific binding of cRNA probes to plaques in two mouse models for AD. The widespread and general staining of the plaques prevented us from studying endogenous expression of cadherins in transgenic brain by in situ hybridization.Electronic supplementary materialThe online version of this article (doi:10.1186/s12952-016-0065-9) contains supplementary material, which is available to authorized users.
Highlights
Alzheimer’s disease (AD) is characterized by the pathological deposition of amyloid-β (Aβ) protein-containing plaques
Cadherin in situ hybridization results in differential plaque staining in AD mouse models We analyzed the expression patterns of several cadherins with antisense cRNA probes
We show exemplary staining patterns only for cadherin-2 (Cdh2), Cdh11, protocadherin-8 (Pcdh8) and Pcdh10 in transgenic 12-months-old Aβ precursor protein (APP)/PS1 mice and wild-type littermates
Summary
Alzheimer’s disease (AD) is characterized by the pathological deposition of amyloid-β (Aβ) protein-containing plaques. Microglia and astrocytes are commonly attracted to the plaques by an unknown mechanism that may involve cell adhesion. One cell adhesion family of proteins, the cadherins, are widely expressed in the central nervous system. Our study was designed to map the expression of cadherins in AD mouse brains. Its pathological hallmarks are plaques and neurofibrillary tangles in the brain. Plaques represent protein accumulations, which mostly contain Aβ peptides. Plaques are surrounded by dying neurons and neuroglia, like microglia and astrocytes [2,3,4]. The mechanism, by which microglia are attracted by aggregated Aβ and attach to the plaques, is unknown. A family of calcium-depended cell adhesion proteins, are
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