Table 1.
Clinical Pathological Correlates of Frontotemporal Lobar Degeneration (FTLD)a
| FTD Organized by Clinical Syndromes | |
|---|---|
| FTD Clinical Syndrome | Typically Associated FTLD Pathology |
| bvFTD | Tau (3R > 4R) ≈ TDP-43 (type A ≥ type B > type D) > (Alzheimer’s pathology) > FUS |
| svPPA | TDP-43 type C > 3R tau |
| nfvPPA | 4R tau (CBD and PSP) > 3R tau and TDP-43 type A |
| FTD-MND | TDP-43 type B > TDP-43 type A > FUS |
| CBS | 4R tau (CBD) > (Alzheimer’s pathology) > PSP, TDP-43 > 3R tau |
| PSP-S | 4R tau (PSP > CBD) |
| FTD Organized by Underlying Pathologies | |
| FTLD Pathology Subtypes (and sites of rare mutations) | Typical FTD Clinical Syndrome |
| FTLD-tau: (MAPT) | |
| 3R tau (Pick’s disease): | bvFTD > nfvPPA, svPPA, CBS |
| 4R tau: | |
| CBD | Motor dysexecutive (including CBS) > PSP-S, nfvPPA, bvFTD |
| PSP | PSP-S > CBS, nfvPPA, bvFTD |
| FTLD-TDP | |
| Type A: (GRN) | bvFTD > CBS, nfvPPA > FTD-MND |
| Type B: (C9ORF72) | bvFTD, FTD-MND, ALS |
| Type C | svPPA |
| Type D (always VCP mutation) | bvFTD, ALS, Paget’s disease of bone, inclusion body myositis |
| FTLD-FUS (FUS gene) | |
| aFTLD-U, BIBD, NIFID | bvFTD if sporadic versus ALS if genetic |
a
FTD, frontotemporal dementia; bvFTD, behavioral-variant FTD; svPPA, semantic-variant primary progressive aphasia; nfvPPA, nonfluent/agrammatic-variant PPA; FTD-MND, FTD motor neuron disease; CBS, corticobasal syndrome; CBD, corticobasal degeneration; PSP, progressive supranuclear palsy; ALS, amyotrophic lateral sclerosis; aFTLD-U, atypical FTLD with ubiquitin inclusions; BIBD, basophilic inclusion body disease; NIFID, neuronal intermediate filament inclusion disease.