Parkinson's Progression Markers Initiative brain autopsy program. (August 2022)

• Record Type: Journal Article
• Authors: Bukhari, Syed A.; Nudelman, Kelly N.H.; Rumbaugh, Malia; Richeson, Pema; Fox, Edward J.; Montine, Kathleen S.; Aldecoa, Iban; Garrido, Alicia; Franz, Jonas; Stadelmann, Christine; Vonsattel, Jean Paul G.; Poston, Kathleen L.; Foroud, Tatiana M.; Montine, Thomas J.
• Is Part Of: Parkinsonism & related disorders. Volume 101(2022)
• Page Start: 62
• Page End: 65
• Publication Date: 2022-08
• Subjects: Parkinson's disease -- Periodicals; Movement disorders -- Periodicals; Movement Disorders -- Periodicals; Nerve Degeneration -- Periodicals; Nervous System Diseases -- Periodicals; Parkinson Disease -- Periodicals; Tremor -- Periodicals; Parkinson, Maladie de -- Périodiques; Parkinson's disease; 616.833
• DOI: 10.1016/j.parkreldis.2022.06.017
• Languages: English
• ISSNs: 1353-8020

Abstract

Abstract: We report on the initial 17 (11 male:6 female) brain autopsies from across Europe and the United States in the Parkinson's Progression Markers Initiative (PPMI). Clinical diagnoses were Parkinson's disease (n = 15), multiple system atrophy (n = 1), and Dementia with Lewy bodies (n = 1); average age of death = 72 ± 8 yr. Cognitive assessment at last evaluation was 5 with normal cognition, 7 with mild cognitive impairment, and 5 with dementia. Genetic assessment showed 4 participants were heterozygous or homozygous for GBA N370S and 3 were heterozygous carriers for LRRK2 R1441G or G2019S; 1 was an APOE ε2 carrier and 5 were APOE ε4 carriers. Longitudinal DAT neuroimaging as well as CSF and plasma biomarker data are summarized. Neuropathologic examination confirmed all clinical diagnoses and showed the expected frequencies of common comorbidities; no evidence of chronic traumatic encephalopathy was observed. Thus, brain autopsy data can provide confirmation, clarification, and new insights into the PD progression observed during life. As it grows, the PPMI brain autopsy program will provide a deeply-annotated research resource to the community of investigators focused on developing biomarkers for PD progression. Highlights: PPMI's first 17 brain donations from enrolled volunteers were characterized. Neuropathologic evaluation confirmed the 15 PD, 1 MSA and 1 DLB clinical diagnoses. Longitudinal decreases in CSF Aβ correlated with greater Aβ plaque in brain. Longitudinal changes in CSF α-syn or total tau were not seen in this small set. LRRK2 and GBA risk variants influenced neuropathologic-cognitive concordance.