Frontotemporal dementia pathology
FTD pathology organized by clinical syndrome
(Ljubenkov and Miller, 2016)
- Behavioral variant frontotemporal dementia:
- Tau (3R > 4R) ≈ TDP-43 (type A ≥ type B > type D) > (Alzheimer’s pathology) > FUS
- Semantic variant primary progressive aphasia
- TDP-43 type C > 3R tau
- Nonfluent / agrammatic variant primary progressive aphasia
- 4R tau (CBD and PSP) > 3R tau and TDP-43 type A
- Frontotemporal dementia-motor neuron disease
- TDP-43 type B > TDP-43 type A > FUS
- Corticobasal syndrome / corticobasal degeneration
- 4R tau (CBD) > (Alzheimer’s pathology) > PSP, TDP-43 > 3R tau
- Progressive supranuclear palsy (Steele-Richardson-Olszewski)
- 4R tau (PSP > CBD)
FTD organized by underlying pathology
(Ljubenkov and Miller, 2016)
- FTLD-tau: (MAPT)
- 3R tau (Pick’s disease)
- bvFTD > nfvPPA, svPPA, CBS
- 4R tau, CBD
- Motor dysexecutive (including CBS) > PSP-S, nfvPPA, bvFTD
- 4R tau, PSP
- PSP-S > CBS, nfvPPA, bvFTD
- 3R tau (Pick’s disease)
- FTLD-TDP
- TDP type A (GRN)
- bvFTD > CBS, nfsvPPA > FTD-MND
- TDP type B (C9ORF72)
- bvFTD, FTD-MND, ALS
- TDP type C
- svPPA
- TDP type D (always VCP mutation)
- bvFTD, ALS, Paget’s disease of the bone, inclusion body myositis
- TDP type A (GRN)
- FTLD-FUS (FUS gene)
- atypical FTLD with ubiquitin inclusions, basophilic inclusion body disease; neuronal intermediate filament inclusion disease
- bvFTD if sporadic (w/ early age of onset (22-46 years) versus ALS if genetic
- atypical FTLD with ubiquitin inclusions, basophilic inclusion body disease; neuronal intermediate filament inclusion disease
References
Ljubenkov, P. A. & Miller, B. L. A Clinical Guide to Frontotemporal Dementias. FOCUS 14, 448–464 (2016). https://pubmed.ncbi.nlm.nih.gov/31975825/
