Genes

Pathology

Notes

MAPT

Tauopathy

Microtubule-associated protein tau mutations cause abnormal tau aggregation. Seen in FTLD-tau.

GRN

TDP-43

Haploinsufficiency leads to decreased progranulin, associated with TDP-43 inclusions (FTLD-TDP).

C9 or f72

TDP-43 + DPRs

Hexanucleotide repeat expansion causes both TDP-43 pathology and toxic dipeptide repeat proteins (DPRs). Very common in FTLD and ALS.

TARDBP

TDP-43

Encodes TDP-43 directly. Mutations promote aggregation and cytoplasmic mislocalization.

FUS

FUS pathology

RNA-binding protein, aggregates directly in some rare forms of FTLD.

VCP

TDP-43

Impairs protein degradation pathways (like autophagy), leading to TDP-43 accumulation.

CHMP2B

Ubiquitin-positive, TDP-43-negative inclusions

Involved in endosomal sorting (ESCRT pathway). Rare cause of FTLD.

TBK1

TDP-43

Impaired autophagy and immune regulation. Mutations linked to FTLD and ALS.

OPTN

TDP-43

Autophagy receptor, linked to FTLD/ALS spectrum.

SQSTM1

TDP-43

Involved in autophagy-lysosome pathway. p62-positive inclusions are common.