Increased norepinephrine‐associated adrenomedullary inclusions in Parkinson's disease

Abstract

The association with Parkinson's disease (PD) of adrenomedullary inclusions, known as 'hyaline globules' or 'adrenal bodies', has been reported for over 35 years. However, the common perception has been that adrenomedullary chromaffin cells cannot be recognized as pathological cells in PD. In the present study, we discovered that the number of adrenomedullary inclusions per unit area of the adrenal medulla was larger in PD and other Lewy body disorders (LBD) than in other neurological diseases and controls without any autonomic dysfunctions, and correlated with the duration of LBD. We also showed that the cells with adrenomedullary inclusions are all norepinephrine-secreting chromaffin cells. This was detected by PAS reaction following peroxidase immunohistochemistry of four proteins: chromogranin A, phenylethanolamine N-methyltransferase, S-100 protein and neurofilament protein. We also proved that the components of adrenomedullary inclusions are immunocytochemically different from those of Lewy bodies and Lewy-related neurites, as adrenomedullary inclusions were immunonegative to ubiquitin and alpha-synuclein as well as to the above four proteins. Therefore, contrary to current opinion, the norepinephrine-secreting adrenomedullary chromaffin cell is indeed another type of pathological cell in PD and other LBD.

New onset atrial fibrillation after patent foramen ovale closure

“…The adrenal gland is evolutionarily related to the sympathetic ganglia, and its capsula contains autonomic nerves and ganglia. There is evidence of involvement of the peripheral ANS in the adrenal gland in PD 89–91. One group reported adrenomedullary inclusions (adrenal bodies) in some patients, which they recognized to be Lewy‐body‐related (though they were also associated with other neurological diseases) 92.…”

Lesions outside the CNS in Parkinson's disease

“…There is evidence of involvement of the peripheral ANS in the adrenal gland in PD. [89][90][91] One group reported adrenomedullary inclusions (adrenal bodies) in some patients, which they recognized to be Lewy-body-related (though they were also associated with other neurological diseases). 92 Lewy-body-related a-synucleinopathy was also detected in the sympathetic ganglia cells and nerve fascicles in the adrenal gland in 11% of 783 general autopsy cases.…”

Adrenal medulla of AS/AGU rats: a histological and immunohistochemical study

“…The sympathetic nervous system has already been recognised as a pathological site in PD [44]. PD is frequently accompanied by a variety of autonomic symptoms.…”

“…It has been shown that the number of adrenomedullary inclusions per unit area of the adrenal medulla in patients complaining of PD and other Lewy body disorders (LBD) was higher compared to other neurological diseases and apparently healthy subjects without any autonomic dysfunctions, and correlated with the duration of LBD. It was reported that the cells which contain adrenomedullary inclusions are all norepinephrine-secreting chromaffin cells [44]. The presence of adrenomedullary inclusions indicates cellular degeneration which may be ascribed to a defect of norepinephrine reuptake and metabolism [47] or due to a long-term acceleration of the secretion of adrenomedullary norepinephrine in PD resulting in high circulating levels of norepinephrine [44].…”

“…It was reported that the cells which contain adrenomedullary inclusions are all norepinephrine-secreting chromaffin cells [44]. The presence of adrenomedullary inclusions indicates cellular degeneration which may be ascribed to a defect of norepinephrine reuptake and metabolism [47] or due to a long-term acceleration of the secretion of adrenomedullary norepinephrine in PD resulting in high circulating levels of norepinephrine [44]. The results of the current study revealed an increase in the number of Lewy's bodies in AS/AGU rats compared to AS rats that proportionally increased with age.…”