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FTDP – 17 without parkinsonism in family with the tau gene (MAPT) mutation
Neurochemical Conference 2009 Oral communications
fected accordingly: SAD, but not FAD cells, had longer G1-phase. These data show that SAD involves G1 prolongation pathway linked to p21, which is not activated in FAD lines. The inhibition of gammasecretase did not change the CC profiles of any of the cell lines indicating that the aberrations observed in
AD cells are induced by factors different than proteolytic products of this enzyme. Altogether, the data show that mechanism of SAD differs from FAD linked to PS1 mutations, and disturbances of CC pathways in lymphocytes might have a diagnostics value.
FTDP – 17 without parkinsonism in family with the tau gene (MAPT) mutation Chodakowska-¯ebrowska Ma³gorzata1, Barczak Anna1, Berdyñski Mariusz2, Sikorska Jolanta1, Barcikowska Maria2 CSK MSWiA Hospital, Warszawa, Poland; Department of Neurodegenerative Disorders, Mossakowski Medical Research Centre Polish Academy of Sciences, Warszawa, Poland e-mail: [email protected] Mutations in the tau gene (MAPT) cause frontotemporal dementia with parkinsonism linked to chromosome 17(FTDP-17). We present results of two members of FTDP-17 family with behavior and cognitive disturbances without parkinsonism. Two brothers, one aged 50 with suspicion of dementia and other, aged 48 with no evident clinical complaints underwent neurological, neuropsychological and MRI examination. We obtained consent and DNA was isolated from blood leukocytes using standard procedure. All MAPT exons with flanking intronic regions were sequenced. Patients’ father, and his two brothers presented behavioral and cognitive deficits about their mid fifties, but were never diagnosed. Neurological examination showed no deficits. In the neuropsychological evaluation cognitive disorders were found, suggesting underlying frontal and temporal pathology. Elder brother presented general dys-
function more apparent in his lack of control and insight, distractibility, executive and language functions deficits, with relatively spared delayed memory. He needs a supervision on activity of daily living. Younger brother showed only discrete, however significant deficits in immediate memory and verbal fluency. Neuroimaging results of elder brother showed asymmetric general cortico-subcortical atrophy, more dominant in the left hippocampus. Younger brother MRI revealed discrete frontal atrophy. Both brothers’ DNA sequence analysis of MAPT revealed a C to T missense mutation in exon 10 causing a proline to leucine change at codon 301 (P301L) in the microtubule binding domain. Further observation of all members of the family is needed. Molecular, neuropsychological and neuroimaging testing is essential in familial neurodegenerative diseases research.
Pharmacological Reports, 2009, 61, 12231235
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fected accordingly: SAD, but not FAD cells, had longer G1-phase. These data show that SAD involves G1 prolongation pathway linked to p21, which is not activated in FAD lines. The inhibition of gammasecretase did not change the CC profiles of any of the cell lines indicating that the aberrations observed in
AD cells are induced by factors different than proteolytic products of this enzyme. Altogether, the data show that mechanism of SAD differs from FAD linked to PS1 mutations, and disturbances of CC pathways in lymphocytes might have a diagnostics value.
FTDP – 17 without parkinsonism in family with the tau gene (MAPT) mutation Chodakowska-¯ebrowska Ma³gorzata1, Barczak Anna1, Berdyñski Mariusz2, Sikorska Jolanta1, Barcikowska Maria2 CSK MSWiA Hospital, Warszawa, Poland; Department of Neurodegenerative Disorders, Mossakowski Medical Research Centre Polish Academy of Sciences, Warszawa, Poland e-mail: [email protected] Mutations in the tau gene (MAPT) cause frontotemporal dementia with parkinsonism linked to chromosome 17(FTDP-17). We present results of two members of FTDP-17 family with behavior and cognitive disturbances without parkinsonism. Two brothers, one aged 50 with suspicion of dementia and other, aged 48 with no evident clinical complaints underwent neurological, neuropsychological and MRI examination. We obtained consent and DNA was isolated from blood leukocytes using standard procedure. All MAPT exons with flanking intronic regions were sequenced. Patients’ father, and his two brothers presented behavioral and cognitive deficits about their mid fifties, but were never diagnosed. Neurological examination showed no deficits. In the neuropsychological evaluation cognitive disorders were found, suggesting underlying frontal and temporal pathology. Elder brother presented general dys-
function more apparent in his lack of control and insight, distractibility, executive and language functions deficits, with relatively spared delayed memory. He needs a supervision on activity of daily living. Younger brother showed only discrete, however significant deficits in immediate memory and verbal fluency. Neuroimaging results of elder brother showed asymmetric general cortico-subcortical atrophy, more dominant in the left hippocampus. Younger brother MRI revealed discrete frontal atrophy. Both brothers’ DNA sequence analysis of MAPT revealed a C to T missense mutation in exon 10 causing a proline to leucine change at codon 301 (P301L) in the microtubule binding domain. Further observation of all members of the family is needed. Molecular, neuropsychological and neuroimaging testing is essential in familial neurodegenerative diseases research.
Pharmacological Reports, 2009, 61, 12231235
#