[Postmortal diagnosis of Parkinson's disease]. / Zur postmortalen Diagnose des idiopathischen Morbus Parkinson.

Parkinson's disease is a continuously progressive degenerative disorder of the central, peripheral and enteric human nervous systems. Not only the substantia nigra, but also a number of other components of the motor and limbic systems, as well as the autonomic regulation, suffer heavy damages. Only a few of the many types of nerve cells in the human central nervous system develop the characteristic Lewy bodies and Lewy neurites. They are composed primarily of aggregated alpha-synuclein and lead to the premature destruction of the affected neurons. Due to the selective neuronal vulnerability, a distinctive distribution of changes occurs within the central nervous system, leading to a corresponding loss of functionality in many systems. The changes occur in an ordered timely fashion. The ascending pathological process begins within the brain at the glossopharyngeal and vagal areas, nearly destroys the substantia nigra, and reaches the mesocortex of the gray matter. From here it expands to further areas of the neocortex, thereby marking the end phase of the disease.

Interstitial cells subjacent to the entorhinal region expressing somatostatin-28 immunoreactivity are susceptible to development of Alzheimer's disease-related cytoskeletal changes.

Interstitial cells are isolated neurons located in the infracortical white matter that are known to express neuropeptides. Twenty-four cases selected for the absence, slight (Braak stages I-II), moderate (Braak stages III-IV), or serious degree (Braak stages V-VI) of cortical neurofibrillary pathology were studied for the presence of Alzheimer's disease-related abnormal tau in interstitial cells of the entorhinal region. AT8-immunoreactive white matter neurons were observed in all Braak stages of cortical neurofibrillary pathology. Both normal-appearing neurons and neurons with degenerative changes in the cellular processes were observed. Normal-appearing cells were predominantly found in stages I and II, whereas degenerative interstitial cells numerically increased from stage I onwards. The normal-appearing cells were medium-sized (10-25 micro m), with ovoid, fusiform, triangular or multipolar cell bodies, and showed an extensive dendritic field, which was oriented perpendicular to the direction of the perforant pathway. Since the morphology of the AT8-immunopositive normal-appearing cells was similar to that reported on somatostatinergic interstitial cells subjacent to the entorhinal region, double-labeling with AT8 and anti-somatostatin-28 (S309) was performed. All AT8-immunoreactive normal-appearing interstitial cells revealed co-staining with somatostatin-28 antiserum, whereas some of the AT8-immunopositive cells with degenerative processes reacted positively and others negatively with S309. In summary, a distinctive interstitial cell type characterized by extensive arborization oriented perpendicular to the course of the perforant pathway and showing somatostatin expression is susceptible to developing the Alzheimer's disease-related cytoskeletal changes. Progression in cytoskeleton change is accompanied by loss of somatostatin.

alpha-synuclein immunopositive Parkinson's disease-related inclusion bodies in lower brain stem nuclei.

Advanced silver stains and immunohistochemical reactions against alpha-synuclein were used to detect Parkinson's disease-related cytoskeletal abnormalities in select lower brain stem nuclei. Various types of inclusion bodies including inconspicuous and heretofore unnoted granular particles and thread-like Lewy neurites were visualized. Of the nuclei investigated (gigantocellular reticular nucleus, bulbar raphe nuclei, coeruleus-subcoeruleus area), only lipofuscin- or neuromelanin-laden neuronal types showed a propensity to develop the pathological changes. Neuronal types devoid of pigment deposits remained free of the cytoskeletal abnormalities. Fine, dust-like particles and small globular Lewy bodies were encountered solely within the limits of intraneuronal lipofuscin or neuromelanin deposits.

Parkinson's disease: affection of brain stem nuclei controlling premotor and motor neurons of the somatomotor system.

Pathological changes which consistently develop in the lower brain stem of patients suffering from Parkinson's disease are described against the background of the internal organization and interconnections of the involved nuclei, i.e., the gigantocellular reticular nucleus, bulbar raphe nuclei, and coeruleus-subcoeruleus area. Immunoreactions against the presynaptic protein alpha-synuclein reveal not only the voluminous forms of Lewy bodies and Lewy neurites but also the otherwise inconspicuous dot- or thread-like types. These lesions develop solely in specific neuronal types. Lipofuscin- or neuromelanin-laden projection cells which at the same time generate a long, unmyelinated or sparsely myelinated axon are particularly susceptible to developing the changes. The bulbar nuclei under consideration receive strong input from supramedullary sources, above all from higher order centers of the limbic system such as the central amygdalar nucleus, periaqueductal gray, and parabrachial nuclei. In turn, they generate descending projections to premotor and motor neurons of the somatomotor system. The disease-related deterioration of both the supramedullary limbic centers and the bulbar brain stem nuclei reduces the limbic influence and markedly impairs the control of premotor and motor neurons. This functional deficit most probably contributes to the overall dysfunction of the motor system typically evolving in the course of Parkinson's disease.

Alpha-synuclein immunoreactive Lewy bodies and Lewy neurites in Parkinson's disease are detectable by an advanced silver-staining technique.

Immunostaining with anti-alpha-synuclein is used to detect Lewy bodies and Lewy neurites in cases of Parkinson's disease and related disorders. To prove that the result of a modern silver method is equivalent to that achieved with immunoreactions for alpha-synuclein, individual sections were successively processed using both methods. The silver-stained sections showed all of the immunoreactive Lewy bodies, and thin Lewy neurites were detected equally well by both techniques. The present study, therefore, points to the capabilities of a modern silver-staining method which is less time consuming and less expensive than immunocytochemical techniques.

Extensive axonal Lewy neurites in Parkinson's disease: a novel pathological feature revealed by alpha-synuclein immunocytochemistry.

Lewy bodies and coarse Lewy neurites are the pathological hallmarks of degenerating neurons in the brains of patients suffering from Parkinson's disease (PD). Recently, the presynaptic protein alpha-synuclein was shown to be a major component of Lewy bodies and Lewy neurites. This study demonstrates for the first time that extensive and thin alpha-synuclein-immunoreactive inclusions are present in the axonal processes of neurons.