Gydesen, S., Brown, J. M., Brun, A., Chakrabarti, L., Gade, A., Johannsen, P., Rossor,
M., Thusgaard, T., Grove, A., Yancopoulou, D., Spillantini, M. G., Fisher, E. M.,
Collinge, J., & Sorensen, S. A. (2002). Chromosome 3 linked frontotemporal dementia
(FTD-3). Neurology, 59, 1585-1594.
Adr.: Frontotemporal Dementia Research in Jutland Association (FreJA), Denmark
BACKGROUND: The authors have identified and studied a large kindred in which
frontotemporal dementia (FTD) is inherited as an autosomal dominant trait. The trait has
been mapped to the pericentromeric region of chromosome 3. METHODS: The authors
report on the clinical, neuroimaging, neuropsychological, and pathologic features in this
unique pedigree collected during 17 years of study. RESULTS: Twenty-two individuals
in three generations have been affected; the age at onset varies between 46 and 65 years.
The disease presents with a predominantly frontal lobe syndrome but there is also
evidence for temporal and dominant parietal lobe dysfunction. Late in the illness
individuals develop a florid motor syndrome with pyramidal and extrapyramidal features.
Structural imaging reveals generalized cerebral atrophy; H2 15 O-PET scanning in two
individuals relatively early and late in the disease shows a striking global reduction in
cerebral blood flow affecting all lobes. On macroscopic pathologic examination, there is
generalized cerebral atrophy affecting the frontal lobes preferentially. Microscopically,
there is neuronal loss and gliosis without specific histopathologic features.
CONCLUSIONS: FTD-3 shares clinical and pathologic features with other forms of FTD
and fulfills international consensus criteria for FTD. There is involvement of the parietal
lobes clinically, radiologically, and pathologically in FTD-3 in contrast to some forms of
FTD. This more diffuse involvement of the cerebral cortex leads to a distinctive, global
pattern of reduced blood flow on PET scanning