Conjugal Synucleinopathies: A Clinicopathologic Study.

BACKGROUND: While preclinical studies have shown that alpha-synuclein can spread through cell-to-cell transmission whether it can be transmitted between humans is unknown. OBJECTIVES: The aim was to assess the presence of a synucleinopathy in autopsied conjugal couples. METHODS: Neuropathological findings in conjugal couples were categorized as Parkinson's disease (PD), dementia with Lewy bodies (DLB), Alzheimer's disease with Lewy bodies (ADLB), incidental Lewy body disease (ILBD), or no Lewy bodies. RESULTS: Ninety conjugal couples were included; the mean age of death was 88.3 years; 32 couples had no Lewy bodies; 42 couples had 1 spouse with a synucleinopathy: 10 PD, 3 DLB, 13 ADLB, and 16 ILBD; 16 couples had both spouses with a synucleinopathy: in 4 couples both spouses had PD, 1 couple had PD and DLB, 4 couples had PD and ADLB, 2 couples had PD and ILBD, 1 couple had DLB and ADLB, in 3 couples both had ADLB, and 1 couple had ADLB and ILBD. No couples had both spouses with ILBD. CONCLUSIONS: This large series of 90 autopsied conjugal couples found 16 conjugal couples with synucleinopathies, suggesting transmission of synucleinopathy between spouses is unlikely. © 2024 International Parkinson and Movement Disorder Society.

Generalization of In-Place Balance Perturbation Training in People With Parkinson Disease.

BACKGROUND AND PURPOSE: Reactive balance training improves reactive postural control in people with Parkinson disease (PwPD). However, the extent to which reactive balance training generalizes to a novel, unpracticed reactive balance task is unknown. This study aimed to determine whether reactive training stepping through support surface translations can be generalized to an unpracticed, instrumented tether-release task. METHODS: Twenty-five PwPD (70.52 years ± 7.15; Hoehn and Yahr range 1-3) completed a multiple baseline, open-label, uncontrolled pre-post intervention study. Stepping was trained through a 2-week (6-session) intervention with repeated support surface translations. Performance on an untrained tether-release task (generalization task) was measured at 2 baseline assessments (B1 and B2, 2 weeks apart), immediately after the intervention (P1), and 2 months after training (P2). The tether-release task outcomes were the anterior-posterior margin of stability (MOS), step length, and step latency during backward and forward steps. RESULTS: After support surface translation practice, tether-release stepping performance improved in MOS, step length, and step latency for both backward and forward steps compared to baseline ( P < 0.05). Improvements in MOS and step length during backward and forward steps in the tether-release task, respectively, were related to stepping changes in the practiced task. However, the improvements in the generalization task were not retained for 2 months. DISCUSSION AND CONCLUSIONS: These findings support short-term generalization from trained balance tasks to novel, untrained tasks. These findings contribute to our understanding of the effects and generalization of reactive step training in PwPD. VIDEO ABSTRACT AVAILABLE: for more insights from the authors (see the Video, Supplemental Digital Content available at http://links.lww.com/JNPT/A465 ).

Symmetry of synuclein density in autopsied Parkinson's disease submandibular glands.

BACKGROUND: Peripheral tissue biopsy in Parkinson's disease (PD) may be valuable for clinical care, biomarker validation, and as research enrollment criteria. OBJECTIVE: Determine whether submandibular gland pathologic alpha-synuclein (aSyn) density is symmetrical and whether previous needle biopsy caused tissue damage. METHODS: Thirty autopsy-confirmed PD cases having fixed submandibular gland tissue from one side and frozen submandibular gland tissue from the contralateral side were studied. Tissue was stained for phosphorylated aSyn and density (0-4 semiquantitative scale) was determined. Three previously biopsied cases were also assessed for tissue damage at subsequent autopsy. RESULTS: Mean (SD) age was 80.9 (5.5) years and disease duration 12.5 (9.3). Submandibular gland aSyn staining had a mean score of 2.13 for both the initially fixed and the initially frozen submandibular glands. The correlation between aSyn density of the two sides was r = 0.63. Correlation of aSyn density, in the originally fixed submandibular gland, with disease duration was good (r = 0.49, p =.006). No permanent tissue damage was found in the three previously biopsied cases. CONCLUSIONS: This study found good correlation between aSyn density in both submandibular glands of patients with PD and found no evidence of significant tissue damage in previously biopsied subjects.

Disease progression modelling reveals heterogeneity in trajectories of Lewy-type α-synuclein pathology.

Lewy body (LB) diseases, characterized by the aggregation of misfolded α-synuclein proteins, exhibit notable clinical heterogeneity. This may be due to variations in accumulation patterns of LB neuropathology. Here we apply a data-driven disease progression model to regional neuropathological LB density scores from 814 brain donors with Lewy pathology. We describe three inferred trajectories of LB pathology that are characterized by differing clinicopathological presentation and longitudinal antemortem clinical progression. Most donors (81.9%) show earliest pathology in the olfactory bulb, followed by accumulation in either limbic (60.8%) or brainstem (21.1%) regions. The remaining donors (18.1%) initially exhibit abnormalities in brainstem regions. Early limbic pathology is associated with Alzheimer's disease-associated characteristics while early brainstem pathology is associated with progressive motor impairment and substantial LB pathology outside of the brain. Our data provides evidence for heterogeneity in the temporal spread of LB pathology, possibly explaining some of the clinical disparities observed in Lewy body disease.

Disease progression modelling reveals heterogeneity in trajectories of Lewy-type α-synuclein pathology.

Lewy body (LB) disorders, characterized by the aggregation of misfolded α-synuclein proteins, exhibit notable clinical heterogeneity. This may be due to variations in accumulation patterns of LB neuropathology. By applying data-driven disease progression modelling to regional neuropathological LB density scores from 814 brain donors, we describe three inferred trajectories of LB pathology that were characterized by differing clinicopathological presentation and longitudinal antemortem clinical progression. Most donors (81.9%) showed earliest pathology in the olfactory bulb, followed by accumulation in either limbic (60.8%) or brainstem (21.1%) regions. The remaining donors (18.1%) exhibited the first abnormalities in brainstem regions. Early limbic pathology was associated with Alzheimer's disease-associated characteristics. Meanwhile, brainstem-first pathology was associated with progressive motor impairment and substantial LB pathology outside of the brain. Our data provides evidence for heterogeneity in the temporal spread of LB pathology, possibly explaining some of the clinical disparities observed in LBDs.