The various staining techniques used by the Tissue Bank not only emphasise the beautiful architecture of the cells within the brain, they also give vital information to the neuropathologist. This allows a definitive diagnosis of the disorder experienced in life by the person who donated tissue. Although we do not exactly know what causes brain cells to die in Parkinson's, the different staining techniques allow us to identify key pathological features associated with cell death in Parkinson's and other disorders. This is just like the "scene of a crime" in that we don’t know who committed the crime but gather evidence such as finger prints, DNA samples etc from the scene which may help us to track down the criminal. In the same way the information we gather on pathological markers in the brain may give clues as to why cells die in Parkinson's. Sections from each donated brain are exposed to a variety of staining techniques, all of which highlight different pathological processes or "clues". The pictures here depict some of these clues.

The first two figures, depict tissue exposed to a traditional stain called Haematoxylin & Eosin that has been used for decades in histology to highlight components of cells and tissue. The Haematoxylin component stains the nuclei of the cell (contains our genetic information) blue and the Eosin stains the rest of the cell shades of pink. The large cells (blue arrow) contains brown granules which help identify dopaminergic neurons/ nerve cells of the substantia nigra, these brown granules are neuromelanin that cause the tissue to appear dark, hence the latin term used for the tissue is nigra or black. The first thing to notice is that in the healthy brain (fig 1) there are considerably more dopaminergic neurons than in the brain from a person with Parkinson's (fig 2).

Secondly, in the Parkinson's brain we detect structures within the dopaminergic neurons that have a pink core and a clear halo (white arrow fig 2). These are Lewy bodies that are thought to be a protective storage site for things like altered/ damaged protein which can be toxic to the cell. Two of the most common altered proteins in the Lewy body are alpha-synuclein and ubiquitin. The full function of these proteins is not fully understood, nor do we understand how the proteins become altered. However, we can visualise such proteins using a modern staining technique called immunocytochemistry, where antibodies with coloured markers can selectively bind to the protein. Fig 3 shows alpha-synuclein staining in the Nucleus Basalis Meynert, another brain area affected in Parkinson's, where you can see the Lewy bodies clearly stained brown (White arrow).

Parkinson's in some cases not only affects the person's ability to move but in certain individuals it can affect their memory, this is similar to the dementia experienced in Alzheimer's disease. Indeed, in some cases we can therefore also detect the “neurofibrilary plaques and tangles” similar to those observed in Alzheimer's brains. Again these structures contain an altered protein, in this case beta-amyloid, which can also be detected by immunocytochemical stains. Fig 4 shows clumps of amyloid within the tissue forming "plaques" of various sizes in the frontal lobe region of the Parkinson's brain.

Neurons are not the only type of cells in the brain, there are also glial cells in the brain that can have "Jekyll & Hyde" type characteristics. They are helpful in maintaining a healthy environment for neurons to survive in and they can remove bits of cell debris when a cell dies. However, when activated they can release chemicals that stimulate a type of inflammatory response that can damage neurons. CR3/43 is a specific antibody that we utilise in immunocytochemical stains which will detect activated glial cells (fig 5 white arrow). There are a number of these activated glial cells in this tissue from a Parkinson's brain, showing evidence of the inflammatory reactions in the tissue.

This article highlights a few of the staining tools that help us in the neuropathological diagnosis of Parkinson's and other pathologies.