De Pablo-Fernandez E, et al. - A neuropathological analysis was carried out of the disease-specific inclusions in the vital structures of the circadian system in patients with Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Findings demonstrated disease-related neuropathological changes in the suprachiasmatic nucleus (SCN) in PD and PSP, but not the pineal gland. It was determined that both the SCN and pineal gland were preserved in MSA, depicting different pathophysiological mechanisms that may indicate significant therapeutic implications.

Methods

• This brain bank case-control study examined the neuropathological inclusions in the SCN of the hypothalamus and pineal gland in healthy controls, PD (Lewy pathology), MSA (glial cytoplasmic inclusions), and PSP (tau inclusions).
• Eligible candidates included 12 healthy control, 28 PD, 11 MSA, and 21 PSP samples from consecutive brain donations (July 1, 2010, to June 30, 2016) to the Queen Square Brain Bank for Neurological Disorders and the Parkinson’s UK Brain Bank, London, United Kingdom.
• Exclusion criteria involved cases where neither SCN nor pineal tissue was available.
• Disease-specific neuropathological changes were graded using a standard semiquantitative scoring system (absent, mild, moderate, severe, or very severe) and compared between groups for the main outcome.

Results

• Owing to the limited tissue availability, the following total samples were assessed in a semiquantitative histologic analysis: 5 SCNs and 7 pineal glands in the control group (6 male; median age at death, 83.8 years; interquartile range [IQR], 78.2-88.0 years), 13 SCNs and 17 pineal glands in the PD group (22 male; median age at death, 78.8 years; IQR, 75.5-83.8 years), 5 SCNs and 6 pineal glands in the MSA group (7 male; median age at death, 69.5 years; IQR, 61.6-77.7 years), and 5 SCNs and 19 pineal glands in the PSP group (13 male; median age at death, 74.3 years; IQR, 69.7-81.1 years).
• There were no neuropathological changes in either the SCN or pineal gland in healthy controls or MSA cases.
• Lewy pathology in the SCN was reported in 9 PD cases and only 2 PD cases had Lewy pathology in the pineal gland.
• As per the data, all PSP cases had inclusions in the SCN, but no PSP cases had pathology in the pineal gland.