Frontotemporal dementia and

McKhann, G. M., Albert, M. S., Grossman, M. et al. Clinical and pathological diagnosis of frontotemporal dementia report of the Work Group on Frontotemporal Dementia and Pick s Disease. Arch. Neurol. 58 1803-1809, 2001. 

On the one hand, the biochemical study of the neuro-pathological lesions led to the identification of their main molecular components. On the other hand, the study of rare, familial forms of Alzheimer s disease, frontotemporal dementia and Parkinson s disease led to the identification of gene defects that cause inherited variants of the different diseases. Remarkably, in these cases, the defective genes have been found to encode or increase the expression of the main components of the neuropathological lesions. It has therefore been established that the basis of the familial forms of these diseases is a toxic property conferred by mutations in the proteins that make up the filamentous lesions. A corollary of this insight is that a similar toxic property may also underlie the much more common, sporadic forms of the diseases. 

Frontotemporal dementias occur as familial forms and, more commonly, as sporadic diseases. They are characterized by a remarkably circumscribed atrophy of the frontal and temporal lobes of the cerebral cortex, often with additional, subcortical changes. In 1994, an autosomal-dominantly inherited form of frontotemporal dementia with parkinsonism was linked to chromosome 17q21.2. Subsequently, other forms of frontotemporal dementia were linked to this region, resulting in the denomination frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) for this class of disease. All cases of FTDP-17 have so far shown a filamentous pathology made of hyperphosphorylated tau protein (Fig. 45-7). In 1998, mutations in tau were reported in FTDP-17 patients [29-31]. Since then, more than 30 different mutations have been described in over 80 families with FTDP-17 (Fig. 45-6). 

Van Swieten, J.C., Rosso, S.M., van Herpen, E., Kamphorst, W., Ravid, R., Heutink, P. (2004) Phenotypic variation in frontotemporal dementia and parkinsonism linked to chromosome 17. Dement. Geriatr. Cogn. Disord., 17, 261-264. 

Ghetti, B., Hutton, M. and Wszolek, Z. (2003) Frontotemporal Dementia and Parkinsonism Linked to chromosome 17 associated with Tau gene mutations (FTDP-17 T), in Neurodegeneration The molecular pathology of dementia and movement disorders (Dickson, D., ed.). ISN Neuropath Press, Basel, pp. 81-155. 

Varani, L., et al (1999). Structure of tau exon 10 splicing regulatory element RNA and destabilization by mutations of frontotemporal dementia and parkinsonism linked to chromosome 17. Proc. Natl. Acad. Sci. USA 96, 8229—8234. 

Wilcock DM, Colton CA (2008) Anti-amyloid-beta immunotherapy in Alzheimer s disease relevance of transgenic mouse studies to clinical trials. J Alzheimers Dis 15 555-569 Wilhamson J, LaRusse S (2004) Genetics and genetic counseling recommendations for Alzheimer s disease, frontotemporal dementia, and Creutzfeldt-Jakob disease. Curr Neurol... 

Bird TD, Nochlin D, Poorkaj P, Chenier M, Kaye J, Payami H et al (1999) A clinical pathological comparison of three families with frontotemporal dementia and identical mutations in the tau gene (P301L). Brain 122(Pt 4) 741-756... 

FTDP-17 frontotemporal dementia and parkinsonism linked to chromosome 17... 

Geser F, Martinez-Lage M, Kwong I.K, Lee, V. M., and Trojanowski JQ. (2009) Amyotrophic lateral sclerosis, frontotemporal dementia and beyond the TDP-43 diseases. J Neurol 256, 1205-1214. 

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