Table 1.
Atlas ROIs with significantly altered volumes in TDP-43Q331K/Q331K mice
| Brain area | Affected brain region (DSURQE mouse brain atlas)23 | Difference in median volume (mm3)/% (false discovery rate adj. P-value) | Equivalent human brain region | Human ALS and FTD imaging evidence |
|---|---|---|---|---|
| Cortex and hippocampus | Accessory olfactory bulb: glomerular, external plexiform and mitral cell layer | −0.05/−9.28 (0.03) | Olfactory bulb (frontal lobe) | No evidence in FTD, only in early AD24 |
| Dorsal taenia tecta | −0.10/−8.52 (0.03) | |||
| Accessory olfactory bulb: granule cell layer | −0.02/−7.24 (0.03) | |||
| Frontal association cortex | −0.79/−9.83 (0.03) | Prefrontal cortex/Frontal lobe | 2 , 25–36 Presymptomatic:4,5,37–39 | |
| Frontal cortex: area 3 | −0.05/−6.61 (0.03) | |||
| Cingulate cortex: area 32 | −0.25/−9.47 (0.03) | Cingulate cortex | 2 , 26 , 27 , 36 Presymptomatic:37–39 | |
| Cingulate cortex: area 24a' | −0.07/−9.59 (0.05) | |||
| Cingulate cortex: area 29a | −0.12/−15.98 (0.03) | |||
| Lateral orbital cortex | −0.30/−9.17 (0.03) | Orbitofrontal cortex | 2 , 25 , 26 , 30 , 32 , 40 Presymptomatic:2,41 | |
| Medial orbital cortex | −0.26/−13.06 (0.03) | |||
| Primary somatosensory cortex | −0.40/−9.74 (0.04) | Somatosensory cortex/parietal lobe | 2 , 26 , 28 , 30 , 35 Presymptomatic:2,4,5,37,39,42 | |
| Caudomedial entorhinal cortex | −0.68/−11.48 (0.02) | Anterior and medial temporal lobe | 2 , 25 , 28–30 , 40 , 43–45 Presymptomatic:2,4,5,37,39,41,42 | |
| Medial entorhinal cortex | −0.07/−10.63 (0.02) | |||
| Ventral intermediate entorhinal cortex | −0.11/−8.99 (0.03) | |||
| CA30r | 0.63/20.66 (0.03) | Hippocampus/temporal lobe | 2 , 26 , 31 , 35 , 36 , 43 , 44 , 46 Presymptomatic4,37,47 | |
| CA3Py Outer | 0.15/16.51 (0.03) | |||
| Pre-para subiculum | −0.22/−9.54 (0.03) | |||
| Subiculum | −0.33/−10.29 (0.03) | |||
| MoDG (dentate gyrus) | −0.40/−10.03 (0.03) | |||
| SLu | 0.06/10.71 (0.05) | |||
| Primary visual cortex: binocular area | −0.21/−10.17 (0.03) | Occipital/posterior cortex | 28 , 30 Presymptomatic:37 | |
| Intermediate nucleus of the endopiriform claustrum | −0.04/−6.99 (0.04) | Piriform cortex | ||
| Subcortical grey matter | Fundus of striatum | −0.01/−7.92 (0.03) | Basal ganglia | 2 , 25 , 28 , 32 , 34 , 36 , 45 , 48 Presymptomatic:47 |
| Lateral septum | 0.48/15.00 (0.03) | Lateral septum | ||
| Claustrum | −0.03/−11.92 (0.03) | Claustrum/insula | ||
| Nucleus accumbens | −0.34/−7.97 (0.03) | Nucleus accumbens/ventral striatum | 25 , 26 , 32 , 45 , 48 Presymptomatic:47 | |
| Thalamus | −1.98/−10.57 (0.03) | Thalamus | 2 , 25 , 26 , 28 , 33 , 35 , 36 , 38 , 49 , 50 Presymptomatic:2,4,5,37,39,42,47 | |
| Basal forebrain | −0.46/−9.59 (0.05) | Basal forebrain | Not reported. Only in MCI51 | |
| Mid-brain | Colliculus: superior | −0.82/−9.03 (0.03) | Superior colliculus | 33 |
| Periaqueductal grey | −0.30/−8.54 (0.03) | Periaqueductal grey | 27 | |
| Colliculus: inferior | −0.64/−10.29 (0.03) | Inferior colliculus | 33 | |
| Brain stem | Medulla | −1.59/−5.17 (0.03) | Medulla | 25 , 26 , 33 |
| Pons | −1.68/−9.26 (0.05) | Pons | ||
| Cerebellum | Flocculus (FL) | −0.10/−12.14 (0.03) | Flocculus | 2 , 25 , 26 , 28 , 30 , 52 , 53 Pre-symptomatic:2,4,37,39,42 |
| Nucleus interpositus | −0.05/−11.83 (0.03) | Nucleus interpositus | ||
| Dentate nucleus | −0.02/−8.81 (0.04) | Dentate nucleus | ||
| Ventricular system | Lateral ventricle | 2.08/57.43 (0.01) | Lateral ventricle | 25 , 31 , 46 , 50 Presymptomatic:47,54 |
| Cerebral aqueduct | −0.05/−15.57 (0.02) | Cerebral aqueduct | ||
| Subependymal zone/rhinocele | −0.005/−9.04 (0.04) | Subependymal zone | ||
| Cerebral white matter | Fimbria | 0.74/23.50 (0.01) | Fimbria | |
| Anterior commissure: pars posterior | −0.04/−9.16 (0.03) | Anterior commissure: pars posterior | ||
| Fasciculus retroflexus | −0.01/−6.87 (0.03) | Fasciculus retroflexus | ||
| Stria medullaris | −0.05/−7.22 (0.03) | Stria medullaris | ||
| Anterior commissure: pars anterior | −0.13/−10.49 (0.04) | Anterior commissure: pars anterior | ||
| Mammilothalamic tract | −0.02/−11.03 (0.04) | Mammilothalamic tract | ||
| Cerebellar white matter | Flocculus white matter | −0.004/−10.37 (0.03) | Flocculus white matter | 26 |
| Cerebellar peduncle: inferior | −0.11/−14.66 (0.03) | Cerebellar peduncles | ||
| Cerebellar peduncle: superior | −0.12/−9.18 (0.03) | |||
| Paraflocculus white matter | −0.03/−13.44 (0.04) | Paraflocculus white matter | ||
| Trunk of arbour vita | −0.47/−9.71 (0.05) | Trunk of arbour vita |
Structures with median volume (mm3) and % difference between TDP43Q331K/Q331K and wildtype mice that are significant at P < 0.05 after false discovery rate correction, and the corresponding or equivalent human brain areas as well evidence of similar/related changes reported in human ALS and FTD imaging literature. Pre-symptomatic: asymptomatic carriers of mutations in C9orf72, MAPT or GRN.