Neuropathological Assessment of Brains Donated to the Parkinson’s Disease Society Tissue Bank

The diagnosis of movement disorders such as idiopathic Parkinson’s disease, multiple system atrophy and progressive supranuclear palsy can be suspected on clinical grounds but it is only with neuropathological examination of brains that a definite diagnosis can be established. Overall, pathological assessment is intended to determine the exact nature of the disease and its severity, evaluate preservation of the tissue, identify co-existent pathologies, and support research studies. To do so, brains donated to the Parkinson’s Disease Society Tissue Bank (PDSTB) are examined by the three members of the Department of Neuropathology of the Imperial College London who examine gross appearance, take samples and do microscopic studies.

Sustantia nigra from a patient with idiopathic Parkinson's disease contains alpha-synuclein positive Lewy bodies.

Macroscopic examination of the whole brain is always mandatory in neuropathology. At the PDSTB this is performed when the organ arrives and includes measure of brain weight, evaluation of meningeal coverings, and evaluation of conformation of gyri, midline structures, cerebellum and vascular structures. When possible, the right half of the brain is frozen and stored and the left half is put in a solution called formalin that preserves the tissue by blocking all processes of degradation. Fixation takes at least 4 weeks and, when it is complete brains are examined again, cut and sampled. Extensive sampling is performed according to a standardised protocol that includes eighteen different regions. Thorough sampling is of paramount importance in the diagnostic procedure because although the characteristic feature of PD is considerable loss of pigmented nerve cells of substantia nigra, equally important is the observation of other structures affected in movement disorders and in other neurodegenerative diseases.

Microscopic studies come after macroscopic examination. Over the last year, neuropathologists and technical staff of the PDSTB have developed a protocol for diagnosing cases. Histological sections are cut from each of the regions sampled and then stained with a routine method for histopathology named haematoxylin-eosin. Haematoxylin-eosin stained sections are reviewed and discussed by neuropathologists and technical staff during weekly meetings in order to look at preservation of the tissue and quality of samples and sections. This step represents a sort of screening because haematoxylin-eosin does not allow recognition of all pathological changes present in neurodegenerative diseases and has to be followed by immunohistochemical reactions. For this, seven selected brain regions are investigated for the presence proteins that may accumulate in movement disorders and other neurodegenerative disorders. These are alpha-synuclein, which is abnormally accumulated in Parkinson’s disease, dementia with Lewy bodies and multiple system atrophy, phosphorylated tau characteristically seen in Alzheimer’s disease and progressive supranuclear palsy and beta-amyloid which is pathologically accumulated in Alzheimer’s disease. In general, microscopic assessment is meant to determine which of the brain structures is involved, the type and amount of protein accumulated and the cell type affected.

Typical tau-positive globoid tangles in dopaminergic neurons in a patient with progressive supranuclear palsy.

At the PDSTB, neuropathological diagnosis is always the result of a close cooperation between neuropathologists and neurologists. The final report is issued only after the cases are reviewed by all the three of the neuropathology team and neuropathological findings subsequently discussed with the referring neurologist. In some instances, additional histochemical and immunohistochemical stains have to be requested, particularly if there are signs or symptoms in the clinical history that require further pathological investigation.

This diagnostic approach to brain donated to the PDSTB takes time but we believe that it guarantees a careful assessment and is therefore of help to support research studies.