Table 4.
Postmortem pathological scoring
| Behavioural impairment | Postmortem assessment of TDP-43 accumulation | |||||||||||||||
| Cell type | Motor | Executive function | Language | Sensory | Other | |||||||||||
| ID | Disease duration | BA4 | BA6 | BA11 | BA24 | BA46 | BA9 | BA44 | BA41 | BA20 | BA39 | BA19 | Ant hip | Post hip | Amygdala | |
| Case 1 | 24 | Neuronal | 1 | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
| Glial | 1 | 1 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | ||
| Case 2 (NEK1) | 159 | Neuronal | 3 | 3 | 1 | 2 | 2 | 2 | 2 | 2 | 2 | 1 | 2 | 3 | 3 | 3 |
| Glial | 3 | 2 | 1 | 1 | 2 | 2 | 2 | 1 | 1 | 1 | 1 | 2 | 2 | 2 | ||
| Case 3 (SOD1) | 98 | Neuronal | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Glial | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
| Executive dysfunction | Postmortem assessment of TDP-43 accumulation | |||||||||||||||
| Cell type | Motor | Executive function | Language | Sensory | Other | |||||||||||
| ID | Disease duration | BA4 | BA6 | BA11 | BA24 | BA46 | BA9 | BA44 | BA41 | BA20 | BA39 | BA19 | Ant hip | Post hip | Amygdala | |
| Case 4 (C9orf72) | 97 | Neuronal | 2 | 1 | 1 | 2 | 1 | 0 | 1 | 1 | 0 | 1 | 0 | 1 | 1 | 1 |
| Glial | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
| Language dysfunction | Postmortem assessment of TDP-43 accumulation | |||||||||||||||
| Cell type | Motor | Executive function | Language | Sensory | Other | |||||||||||
| ID | Disease duration | BA4 | BA6 | BA11 | BA24 | BA46 | BA9 | BA44 | BA41 | BA20 | BA39 | BA19 | Ant hip | Post hip | Amygdala | |
| Case 5 (C9orf72) | 58 | Neuronal | 2 | 2 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | |
| Glial | 3 | 2 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | |||
| Case 6 (C9orf72) | 58 | Neuronal | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Glial | 2 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | ||
| Case 7 | 17 | Neuronal | 3 | 0 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 |
| Glial | 3 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | ||
| Case 8 (C9orf72) | 60 | Neuronal | 3 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 |
| Glial | 3 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | ||
| Case 9 | 150 | Neuronal | 2 | 1 | 0 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 |
| Glial | 2 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | ||
| Case 10 | 13 | Neuronal | 3 | 2 | 1 | 2 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 |
| Glial | 3 | 2 | 1 | 2 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | ||
| Fluency dysfunction | Postmortem assessment of TDP-43 accumulation | |||||||||||||||
| Cell type | Motor | Executive function | Language | Sensory | Other | |||||||||||
| ID | Disease duration | BA4 | BA6 | BA11 | BA24 | BA46 | BA9 | BA44 | BA41 | BA20 | BA39 | BA19 | Ant hip | Post hip | Amygdala | |
| Case 11 | 14 | Neuronal | 2 | 3 | 3 | 3 | 3 | 3 | 2 | 2 | 2 | 2 | 2 | 3 | 3 | |
| Glial | 2 | 3 | 2 | 3 | 2 | 2 | 1 | 2 | 2 | 2 | 2 | 2 | 2 | |||
| Case 12 | 99 | Neuronal | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Glial | 2 | 2 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 2 | 1 | 0 | 0 | 0 | ||
| Combined deficit: executive, language and fluency | Postmortem assessment of TDP-43 accumulation | |||||||||||||||
| Cell type | Motor | Executive function | Language | Sensory | Other | |||||||||||
| ID | Disease duration | BA4 | BA6 | BA11 | BA24 | BA46 | BA9 | BA44 | BA41 | BA20 | BA39 | BA19 | Ant hip | Post hip | Amygdala | |
| Case 13 | 20 | Neuronal | 1 | 2 | 2 | 2 | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 2 | 2 | 2 |
| Glial | 1 | 2 | 2 | 2 | 2 | 2 | 1 | 1 | 2 | 1 | 1 | 2 | 2 | 1 | ||
| Case 14 | 130 | Neuronal | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 2 | 1 | 0 | 2 | 1 | 1 |
| Glial | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 2 | 1 | 0 | 2 | 1 | 1 | ||
| Unimpaired | Postmortem assessment of TDP-43 accumulation | |||||||||||||||
| Cell type | Motor | Executive function | Language | Sensory | Other | |||||||||||
| ID | Disease duration | BA4 | BA6 | BA11 | BA24 | BA46 | BA9 | BA44 | BA41 | BA20 | BA39 | BA19 | Ant hip | Post hip | Amygdala | |
| Case 15 (C9orf72) | 109 | Neuronal | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
| Glial | 2 | 2 | 1 | 1 | 2 | 2 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | ||
| Case 16 | 134 | Neuronal | 1 | 2 | 1 | 1 | 2 | 1 | 2 | 1 | 1 | 1 | 1 | 2 | 2 | 2 |
| Glial | 1 | 2 | 1 | 1 | 2 | 1 | 2 | 1 | 1 | 1 | 1 | 2 | 2 | 2 | ||
| Case 17 | 30 | Neuronal | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Glial | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
| Case 18 | 16 | Neuronal | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 1 |
| Glial | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 1 | ||
| Case 19 (NEK1) | 119 | Neuronal | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Glial | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
| Case 20 | 54 | Neuronal | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Glial | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | ||
| Case 21 | 46 | Neuronal | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Glial | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | ||
| Case 22 | 31 | Neuronal | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Glial | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | ||
| Case 23 (C9orf72) | 33 | Neuronal | 2 | 2 | 1 | 2 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
| Glial | 2 | 2 | 0 | 2 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | ||
| Case 24 | 64 | Neuronal | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Glial | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
| Case 25 | 45 | Neuronal | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Glial | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
| Case 26 (SOD1) | 67 | Neuronal | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Glial | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
| Case 27 | 16 | Neuronal | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Glial | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
Summary of post-mortem TDP-43 pathology for each patient in the cohort, subdivided by ECAS subdomain deficits. Brain regions are grouped by function into: (1) motor, (2) executive function, (3) language, (4) fluency—which is composed of three regions: BA9, BA44 and BA41 with overlap in both language and fluency domains, (5) sensory and (6) other. 0=no TDP-43 pathology identified, 1=mild TDP-43 pathology, 2=moderate TDP-43 pathology and 3=severe TDP-43 pathology. All cases were investigated for genetic diagnoses by either whole genome sequencing or repeat-prime PCR (for C9orf72 status), and mutations are indicated in brackets after the case number.
ECAS, Edinburgh Cognitive and Behavioural Amytrophic lateral sclerosis Screen; TDP-43, 43 kDa Tar-DNA binding protein.