Table 3.
Comparisons between neurodegenerative characteristics associated with mutations in microtubule associated protein tau (MAPT) and progranulin (PGRN)
| MAPT | PGRN | |
|---|---|---|
| Frequency among FTD subjects | 6% | 5% |
| Mode of inheritance | AD | AD |
| Penetrance | >95% | 90% by age 70 |
| Gender | M=F | M=F |
| Onset age | 25-65 | 45-85 |
| Duration of illness | 3-10 years | 1-15 years |
| Clinical features | ||
| Personality/behavior changes | ++++ | ++++ |
| Executive dysfunction | ++++ | ++++ |
| Language impairment | ++++ | ++++ |
| Memory impairment | ++ | ++ |
| Visuospatial impairment | + | ++ |
| Limb apraxia | + | ++ |
| Parkinsonism | ++ | +++ |
| Motor neuron disease | + | 0 |
| Clinical syndromes | ||
| Frontotemporal dementia +/- park | ++++ | ++++ |
| Progressive nonfluent aphasia | ++ | +++ |
| Semantic dementia | + | + |
| Amnestic mild cognitive impairment | + | + |
| Probable Alzheimer’s disease | + | ++ |
| Corticobasal syndrome | + | +++ |
| Posterior cortical atrophy | 0 | 0 |
| Parkinson’s disease | 0 | + |
| Parkinson’s disease +dementia | 0 | + |
| Dementia with Lewy bodies | 0 | + |
| Amyotrophic lateral sclerosis | ++ | 0 |
| Magnetic resonance imaging findings | ||
| Frontal atrophy | ++++ | ++++ |
| Temporal atrophy | +++ | +++ |
| Parietal atrophy | + | ++ |
| Occipital atrophy | 0 | 0 |
| Parenchymal signal changes | + | ++ |
| Pathologic findings | ||
| Tau-positive inclusions | ++++ | + |
| Ubiquitin-positive inclusions | + | ++++ |
| Mechanism of neurodegeneration | altered tau | loss of progranulin |
| Potential treatments | alter protein-protein interactions |
replace or increase progranulin |
++++ = very frequently reported, +++ = frequently reported, ++ infrequently reported, + = extremely rare, 0 = no definite cases reported to date