Table 1.
Disease | Predominant pathology | Co-occurrence of TDP-43 pathology |
Associated genes |
Classic ALS | TDP-43 | n.a. | ALS2, SETX, TARDBP, VAPB, ANG, UBQLN2, OPTN, PFN1, UNC13a, NEK1, C21orf2, SIGMAR1, DCTN1, MATR3, VCP, hnRNPA1/A2b1, NIPA1, TBK1, ATXN2, UBQLN2, SQSTM1 |
Familial ALS-SOD1 | SOD1 | Rarely | SOD1 |
Familial ALS-FUS | FUS | No | FUS |
ALS-FTLD, ALS-ci/bi | TDP-43 | n.a. | TARDBP, CHMP2b, TBK1, UBQLN2, SQSTM1, DCTN1, UNC13a |
Classic ALS, ALS-FTLD, FTLD | TDP-43 | n.a. | C9orf72 |
MSP* | TDP-43 | n.a. | VCP, hnRNPA1, hnRNPA2b1, SQSTM1 |
FTLD | TDP-43 | n.a. | CHMP2b, GRN, SQSTM1, OPTN, TBK1, ATXN2 |
FTLD | FUS | No | – |
FTLD | Tau | No | MAPT |
Alzheimer’s disease | β-Amyloid, tau | Yes | APOE, APP, PSEN1, PSEN2 |
Dementia with Lewy bodies | α-Synuclein | Yes | SNCA, APP, PSEN1/PSEN2, MAPT, GBA, APOE |
Parkinson disease | α-Synuclein | Yes | TARDBP, SNCA, Parkin, PINK1, DJ-1, LRRK2, ATP13A2, PLA2G6 |
Huntington disease | Huntingtin protein | yes | Huntingtin |
LATE/CARTS | TDP-43, HS | n.a. | GRN, TMEM106B, ABCC9, KCNMB2, APOE |
CTE | Tau | Yes | – |
Perry disease | TDP-43 | n.a. | DCTN1 |
FOSMN | TDP-43 | n.a. | SOD1, SQSTM1, VCP, CHCHD10 |
sIBM | TDP-43 | n.a. | – |
PSP | Tau | Yes | MAPT, STX6, EIF2AK3 |
CBD | Tau | Yes | MAPT |
AGD | Tau | Yes | – |
*Multiple system proteinopathy-A familial disorder in which patients present with ALS, FTLD, inclusion body myositis, Paget’s disease of the bone or combinations of these phenotypes.
ALS, amyotrophic lateral sclerosis; bi, behavioural impairment; CARTS, cerebral age-related TDP-43 with sclerosis; ci, cognitive impairment; CTE, chronic traumatic encephalopathy; FOSMN, facial onset sensory and motor neuronopathy; FTLD, frontotemporal lobar degeneration; HS, hippocampal sclerosis; LATE, limbic-predominant age-related TDP-43 encephalopathy; n.a., not applicable; PPA, primary progressive aphasia; sIBM, sporadic inclusion body myositis; TDP-43, TAR DNA-binding protein 43.