TY - JOUR
T1 - Frontotemporal lobar degeneration
T2 - Current knowledge and future challenges
AU - Cerami, Chiara
AU - Scarpini, Elio
AU - Cappa, Stefano F.
AU - Galimberti, Daniela
PY - 2012/11
Y1 - 2012/11
N2 - Frontotemporal lobar degeneration (FTLD) is one of the most frequent neurodegenerative disorders with a presenile onset. It presents with a spectrum of clinical manifestations, ranging from behavioral and executive impairment to language disorders and motor dysfunction. New diagnostic criteria identified two main cognitive syndromes: behavioral variant frontotemporal dementia (bvFTD) and primary progressive aphasia. Regarding bvFTD, new criteria include the use of biomarkers. According to them, bvFTD can be classified in "possible" (clinical features only), "probable" (inclusion of imaging biomarkers) and "definite" (in the presence of a known causal mutation or at autopsy). Familial aggregation is frequently reported in FTLD, and about 10 % of cases have an autosomal dominant transmission. Microtubule-associ-ated protein tau gene mutations have been the first ones identified, and are generally associated with early onset (40-50 years) and with the bvFTD phenotype. More recently, progranulin gene mutations were recognized in association with the familial form of FTLD and a hexa-nucleotide repetition in C9ORF72 has been shown to be responsible for familial FTLD and amyotrophic lateral sclerosis. In addition, other genes are linked to rare cases of familiar FTLD. Lastly, a number of genetic risk factors for sporadic forms have also been identified.
AB - Frontotemporal lobar degeneration (FTLD) is one of the most frequent neurodegenerative disorders with a presenile onset. It presents with a spectrum of clinical manifestations, ranging from behavioral and executive impairment to language disorders and motor dysfunction. New diagnostic criteria identified two main cognitive syndromes: behavioral variant frontotemporal dementia (bvFTD) and primary progressive aphasia. Regarding bvFTD, new criteria include the use of biomarkers. According to them, bvFTD can be classified in "possible" (clinical features only), "probable" (inclusion of imaging biomarkers) and "definite" (in the presence of a known causal mutation or at autopsy). Familial aggregation is frequently reported in FTLD, and about 10 % of cases have an autosomal dominant transmission. Microtubule-associ-ated protein tau gene mutations have been the first ones identified, and are generally associated with early onset (40-50 years) and with the bvFTD phenotype. More recently, progranulin gene mutations were recognized in association with the familial form of FTLD and a hexa-nucleotide repetition in C9ORF72 has been shown to be responsible for familial FTLD and amyotrophic lateral sclerosis. In addition, other genes are linked to rare cases of familiar FTLD. Lastly, a number of genetic risk factors for sporadic forms have also been identified.
KW - C9ORF72
KW - Frontotemporal lobar degeneration
KW - Genetics
KW - Progranulin (GRN)
KW - Risk factor
KW - Tau
UR - http://www.scopus.com/inward/record.url?scp=84868204382&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84868204382&partnerID=8YFLogxK
U2 - 10.1007/s00415-012-6507-5
DO - 10.1007/s00415-012-6507-5
M3 - Article
C2 - 22532172
AN - SCOPUS:84868204382
VL - 259
SP - 2278
EP - 2286
JO - Journal of Neurology
JF - Journal of Neurology
SN - 0340-5354
IS - 11
ER -