Table 1. Comparison of features in familial dementias: frontotemporal lobar degeneration, Alzheimer's disease and prion disease.
Genetic mutation |
Presenting syndrome |
Behavioral and cognitive features | Parkinsonism | Motor neuron disease |
Other clinical features |
Neuroimaging features |
---|---|---|---|---|---|---|
GRN | bvFTLD PNFA CBS |
Behavioral syndrome (apathy, sweet tooth, etc.), executive dysfunction, episodic memory impairment, aphasia, parietal lobe dysfunction |
+ | Rare | Features of CBS can be present |
Often asymmetrical frontal, temporal and parietal lobe atrophy |
MAPT | bvFTLD CBS PSP |
Behavioral syndrome (disinhibition, inappropriate social behaviour, etc.), executive dysfunction, decreased speech, anomia |
+ | − | Features of CBS or PSP can be present |
Bilateral frontotemporal lobar atrophy |
VCP | bvFTLD | Behavioral syndrome, executive dysfunction |
− | − | Inclusion body myopathy and Paget's disease |
A few reports of frontotemporal lobar atrophy |
CHMP2B | bvFTLD |
Behavioral syndrome (apathy, restlessness, aggression etc.), executive dysfunction, decreased speech, can have early parietal impairment |
− | Rare | None | Generalized atrophy |
Chr 9 FTD- MNDa |
bvFTLD MND |
Behavioral syndrome, executive dysfunction |
− | + | None | Single report of frontal lobe atrophy sparing posterior regions |
APP, PS1, PS215 |
AD (i.e. amnestic presentation) Atypical ADb |
Episodic memory impairment initially then global impairment |
Rare | − | Myoclonus or seizures can occur. Spastic paraparesis is seen rarely in PS1. |
Presymptomatic medial temporal lobe atrophy spreading to diffuse neocortical areas |
PRNP16 | Dementia with neurological signs |
Highly heterogenous, ranging from rapidly progressive dementia with myoclonus and ataxia, similar to classical CJD, to much more slowly progressive syndromes involving episodic memory, executive dysfunction, dyspraxia |
+ | Rare | Ataxia, myoclonus, seizures, chorea, or dystonia |
Generalized cerebral and cerebellar atrophy typical. Rapidly progressive clinical syndromes can be associated with high signal in the caudate and putamen on T2-weighted MRI |
A locus on chromosome 9p has been associated with FTD-MND but the abnormal gene has yet to be found.
Rarely, a prominent behavioral phenotype similar to bvFTLD is seen in patients with PS1 mutations.
Abbreviations: AD, Alzheimer's disease; APP, amyloid precursor protein; bvFTLD, behavioral variant frontotemporal lobar degeneration; CBS, corticobasal syndrome; CHMP2B, chromatin-modifying protein 2B; Chr 9 FTD-MND, chromosome 9-associated frontotemporal dementia with motor neuron disease; CJD, Creutzfeldt-Jakob disease; GRN, progranulin, MAPT, microtubule-associated protein tau; PNFA, progressive nonfluent aphasia; PRNP, prion protein, PS1, presenilin 1; PS2, presenilin 2; PSP, progressive supranuclear palsy, VCP, valosin-containing protein; +, can be present; −, absent