Table 1.
Clinical, demographic, genetic and neuropathological features of cases with mixed FTLD-TDP and FTLD-tau pathology
| Case 1 | Case 2 | Case 3 | Case 4 | Case 5 | Case 6 | Case 7 | Case 8 | Case 9 | |
|---|---|---|---|---|---|---|---|---|---|
| Clinical syndrome | bvFTD | bvFTD-MND | svPPA | svPPA (right predominant) | svPPA | CBS | nfvPPA | nfvPPA | bvFTD |
| Sex | Male | Male | Female | Male | Male | Female | Male | Female | Male |
| Age at death | 70 | 77 | 69 | 76 | 85 | 71 | 63 | 72 | 60 |
| Age at onset | 62 | 57 | 65 | 71 | 77 | 65 | 53 | 63 | 56 |
| Disease duration | 8 | 20 | 4 | 5 | 8 | 6 | 10 | 9 | 4 |
| Handedness | Left | Right | Right | Left | Right | Right | Right | Right | Right |
| Education | 12 | 14 | 18 | 20 | 16 | 17 | 16 | 14 | 13 |
| First symptoms | Loss of problem solving, language deterioration | Mental rigidity, compulsion, disinhibition | Word finding troubles, Loss of word meaning | Personality changes | Naming difficulties | Rapidly progressive parkinsonism | Phonemic paraphasia, agrammatism, sound distortion | Word finding difficulties, effortful speech, agrammatism | Behavioral change and cognitive dysfunction |
| Family History for dementia or parkinson’s disease | - | + (mother, other close relatives from the maternal side) | + (father, three siblings with AD type dementia) | - | + | + (Paternal grandmother with dementia with parkinsonian symptoms) | + (paternal uncle and maternal grandmother with parkinson’s disease) | + (mother’s side with AD) | - |
| Parkinsonism and other motor symptoms | + (Masked face, reduced blink frequency) | - | - | + (Bradykinesia, tremor, stooped posture, shuffling gait) | + (Gait unsteadiness) | + (Axial and appendicular rigidity) | + (tremor) | - | + (slowing and shuffling gait) |
| Motor weakness (motor symptoms) | - | + | - | - | - | - | - | - | - |
| APOE | ԑ3/ԑ3 | ԑ3/ԑ3 | ԑ3/ԑ4 | ND | ԑ3/ԑ3 | ND | ԑ3/ԑ3 | ԑ3/ԑ4 | ԑ3/ԑ4 |
| Tau Haplotype | H2/H2 | H1/H2 | H1/H1 | ND | H1/H2 | ND | H1/H1 | H1/H1 | NA |
| MAPT | Negative | Negative | Negative | ND | Negative | ND | A152T | Negative | Negative |
| C9ORF72 | Positive | Negative | Negative | ND | Negative | ND | Negative | Negative | Negative |
| GRN | Negative | Negative | Negative | ND | Negative | ND | Negative | Negative | Negative |
| TARDBP | Negative | A90V | Negative | ND | Negative | ND | Negative | Negative | Negative |
| PSEN1 | Negative | Negative | Negative | ND | Negative | ND | Negative | Negative | Negative |
| APP | Negative | Negative | Negative | ND | Negative | ND | Negative | Negative | Negative |
| Neuropathological change | |||||||||
| Brain Weight (g) | 1066 | 1312 | 1213 | 1250 | 1083 | 1205 | 1545 | 1005 | 1460 |
| ADNC | Low (A1B2C0) | Low (A1B1C0) | Low (A1B1C0) | Low (A1B0C0) | Low (A0B1C0) | Intermediate (A3B2C2) | Low (A1B2C0) | Intermediate* (A2B2C3) | Intermediate (A1B3C3) |
| Synucleinopathy | - | + (brainstem and amygdala) | - | - | + (amygdala only) | + | +* (substantia nigra) | - | - |
| Primary pathological Diagnosis | FTLD-TDP, type A | FTLD-TDP, type B | FTLD-TDP, type B | FTLD-TDP, type C | FTLD-TDP, type C | FTLD-Tau, CBD | FTLD-Tau, CBD | FTLD-Tau, CBD | FTLD-Tau, CBD |
| Contributing pathological Diagnosis | Unclassifiable FTLD-tau | Unclassifiable FTLD-tau | Unclassifiable FTLD-tau | FTLD-Tau, PSP | FTLD-Tau, PSP | FTLD-TDP, type B | Unclassifiable FTLD-TDP** AGD | FTLD-TDP, type A | Unclassifiable FTLD TDP** |
Abbreviations. ADNC: alzheimer’s disease neuropathological change, AGD: argyrophilic grain disease, APOE: apolipoprotein E gene, APP: amyloid precursor protein gene, bvFTD: behavioral variant of frontotemporal dementia, CBD: corticobasal degeneration, CBS: corticobasal syndrome, C9ORF72: chromosome 9 open reading frame 72 gene, FTLD: frontotemporal lobar degeneration, GRN: progranulin, MAPT: microtubule- associated protein tau gene, ND: not done, nfvPPA: nonfluent variant of primary progressive apahsia, PSEN1: presenilin-1, PSP: progressive supranuclear palsy, svPPA: semantic variant of primary progressive aphasia, TARDBP: TAR-DNA binding protein 43 gene
contributing diagnosis
with atypical hippocampal sclerosis