Short biotinylated oligonucleotides bind non-specifically to senile plaques of Alzheimer's disease

We have used in situ hybridization with biotinylated oligonucleotide (antisense) probes and streptavidin-biotinylated alkaline phosphatase method to detect the amount of amyloid beta-protein mRNA in the paraffin-embedded and formalin-fixed brain samples of patients affected by Alzheimer's disease and those of non-affected controls. Instead of the expected specific binding to neuronal cytoplasm, the probes did constantly bind to neuritic senile plaques, the strongest binding being found in the hippocampus and the cerebral cortex. We have been able to constantly repeat this peculiar phenomenon with other (30-mer) oligonucleotide probes, e.g. the sense probes for beta-amyloid protein and those specific for human papillomavirus (HPV) 18- and c-erb B-2 mRNAs. Replacing the probe with water as a negative control lead to abolishment of the colour reaction, thus excluding the possibility of the non-specific staining being due to the detection system. This confirms that the oligonucleotide probe is essential for this binding phenomenon.