Table 1.
Clinical and pathological features of controls, essential tremor, Parkinson’s disease, multiple system atrophy, and spinocerebellar ataxia type 1 cases
| Controls | PD cases | ET cases | MSA cases | SCA1 cases | p value | |
|---|---|---|---|---|---|---|
| n | 25 | 10 | 20 | 10 | 10 | |
| Age at death (years) | 74.7 ± 14.0 | 72.8 ± 7.5 | 85.2 ± 6.2 | 66.8 ± 5.4 | 61.6 ± 7.1 | <0.001a |
| 82.9 ± 4.5 | p = 0.23b | |||||
| Old (n = 15) | ||||||
| 62.3 ± 14.5 | p = 0.37b | p = 0.89b | ||||
| Young (n = 10) | ||||||
| Female sex | 11 (44.0 %) | 2 (20.0 %) | 13 (65.0 %) | 6 (60.0 %) | 3 (30.0 %) | 0.12c |
| Postmortem interval (hours) | 11.5 ± 13.0 (Median = 5.7) | 4.0 ± 4.1 (Median = 2.3) | 2.7 ± 1.9 (Median = 2.4) | 3.5 ± 3.0 (Median = 2.9) | 15.5 ± 8.8 (Median = 16.5) | <0.001d |
| Braak AD stage | N/A | 0.11c | ||||
| 0 | 9 (36.0 %) | 2 (20.0 %) | 1 (5.0 %) | 5 (50.0 %) | ||
| I | 7 (28.0 %) | 1 (10.0 %) | 3 (15.0 %) | 4 (40.0 %) | ||
| II | 6 (24.0 %) | 3 (30.0 %) | 7 (35.0 %) | 0 (0.0 %) | ||
| III | 2 (8.0 %) | 2 (20.0 %) | 7 (35.0 %) | 1 (10.0 %) | ||
| IV | 1 (4.0 %) | 1 (10.0 %) | 1 (5.0 %) | 0 (0.0 %) | ||
| V | 0 (0.0 %) | 1 (10.0 %) | 1 (5.0 %) | 0 (0.0 %) | ||
| VI | 0 (0.0 %) | 0 (0.0 %) | 0 (0.0 %) | 0 (0.0 %) | ||
| CERAD plaque score | N/A | 0.13c | ||||
| 0 | 17 (68.0 %) | 6 (60.0 %) | 8 (40.0 %) | 9 (100.0 %)g | ||
| A | 6 (24.0 %) | 2 (20.0 %) | 7 (35.0 %) | 0 (0.0 %) | ||
| B | 2 (8.0 %) | 2 (20.0 %) | 3 (15.0 %) | 0 (0.0 %) | ||
| C | 0 (0.0 %) | 0 (0.0 %) | 2 (10.0 %) | 0 (0.0 %) | ||
| Purkinje cell counts | 11.3 ± 2.0 | 11.0 ± 3.0e | 8.7 ± 1.4e,**** | 6.0 ± 3.0e,**** | 5.8 ± 2.0e,**** | <0.001a |
| Torpedo counts | 5.8 ± 8.1 (Median = 3.0) | 8.8 ± 6.3f,** (Median = 8.5) | 12.7 ± 8.8f,*** (Median = 15.0) | 106.0 ± 80.0f,**** (Median = 105.0) | 47.9 ± 39.2f,**** (Median = 39.0) | <0.001d |
| CF synaptic density (puncta/100 μm) | 23.8 ± 3.6 | 23.9 ± 5.0e | 20.1 ± 2.7e,*** | 17.2 ± 4.1e,**** | 16.6 ± 2.5e,**** | <0.001a |
| Percentage of CF extending into outer 20 % ML | 16.4 ± 5.4 | 25.1 ± 6.4e,**** | 27.4 ± 7.6e,**** | 8.6 ± 5.4e,*** | 5.1 ± 1.8e,**** | <0.001a |
| CF length in outer 20 % ML (μm) | 1.8 ± 1.2 (Median = 1.4) | 3.6 ± 1.4f,**** (Median = 3.2) | 9.2 ± 5.6f,**** (Median = 7.0) | 0.5 ± 0.6f,**** (Median = 0.2) | 0.8 ± 0.7f,** (Median = 0.6) | <0.001d |
| CF synaptic number in outer 20 % ML | 2.5 ± 1.6 (Median = 2.2) | 5.5 ± 3.0f,**** (Median = 4.6) | 9.7 ± 4.8f,**** (Median = 8.9) | 1.0 ± 1.5f,*** (Median = 0.2) | 1.5 ± 1.9f,* (Median = 0.8) | <0.001d |
| CF branches in outer 20 % ML | 0.1 ± 0.1 (Median = 0.1) | 0.2 ± 0.1f,**** (Median = 0.2) | 0.8 ± 0.6f,**** (Median = 0.7) | 0.0 ± 0.0f,* (Median = 0.0) | 0.1 ± 0.2 (Median = 0.1) | <0.001d |
| Percentage of CF synapses on the thin PC dendritic branchlets | 13.8 ± 6.6 | 22.3 ± 4.8e,* | 34.4 ± 11.8e,**** | N/A | N/A | <0.001a |
Values represent mean ± standard deviation or number (percentage), and for variables with non-normal distribution, the Median is reported as well
Since essential tremor (ET) cases had much older age of death than spinocerebellar ataxia type 1 (SCA1) cases, we selected 15 older controls to match with 20 ET cases and 10 younger controls to match with 10 SCA1 cases to study climbing fiber synaptic pathology during aging
AD Alzheimer’s disease, CERAD the Consortium to establish a Registry for Alzheimer’s disease, CF climbing fiber, ET essential tremor, ML molecular layer, MSA multiple system atrophy, N/A not available, PC Purkinje cells, PD Parkinson’s disease, SCA1 spinocerebellar ataxia type 1, VGlut2 vesicular glutamate transporter type 2
p < 0.05,
p < 0.01,
p < 0.005,
p < 0.001, when compared to controls
One-way analysis of variance (ANOVA)
2 independent samples t test
Chi-square test
Kruskal-Wallis test
Analysis of variance followed by LSD post hoc analyses
Mann-Whitney U test
One data point missing