Alzheimer disease-like clinical phenotype in a family with FTDP-17 caused by a MAPT R406W mutation

S.G. Lindquist; I.E. Holm; M. Schwartz; I. Law; J. Stokholm; M. Batbayli; Gunhild Waldemar; J.E. Nielsen

doi:10.1111/j.1468-1331.2008.02069.x

Alzheimer disease-like clinical phenotype in a family with FTDP-17 caused by a MAPT R406W mutation

S.G. Lindquist, I.E. Holm, M. Schwartz, I. Law, J. Stokholm, M. Batbayli, Gunhild Waldemar, J.E. Nielsen

57 Citationer (Scopus)

Abstract

We report clinical, molecular, neuroimaging and neuropathological features of a Danish family with autosomal dominant inherited dementia, a clinical phenotype resembling Alzheimer's disease and a pathogenic mutation (R406W) in the microtubule associated protein tau (MAPT) gene. Pre-symptomatic and affected family members underwent multidisciplinary (clinical, molecular, neuroimaging and neuropathological) examinations. Treatment with memantine in a family member with early symptoms, based on the clinical phenotype and the lack of specific treatment, appears to stabilize the disease course and increase the glucose metabolism in cortical and subcortical areas, as determined by serial [F(18)]FDG-PET scanning before and after initiation of treatment. Neuropathological examination of a second affected and mutation-positive family member showed moderate atrophy of the temporal lobes including the hippocampi. Microscopy revealed abundant numbers of tau-positive neurofibrillary tangles in all cortical areas and in some brainstem nuclei corresponding to a diagnosis of frontotemporal lobe degeneration on the basis of a MAPT mutation. The clinical and genetic heterogeneity of autosomal dominant inherited dementia must be taken into account in the genetic counselling and genetic testing of families with autosomal dominantly inherited dementia in general
Udgivelsesdato: 2008/4

Originalsprog	Engelsk
Tidsskrift	European Journal of Neurology
Vol/bind	15
Udgave nummer	4
Sider (fra-til)	377-385
Antal sider	8
ISSN	1351-5101
DOI	https://doi.org/10.1111/j.1468-1331.2008.02069.x
Status	Udgivet - 2008

Adgang til dokumentet

10.1111/j.1468-1331.2008.02069.x

Citationsformater

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title = "Alzheimer disease-like clinical phenotype in a family with FTDP-17 caused by a MAPT R406W mutation",

abstract = "We report clinical, molecular, neuroimaging and neuropathological features of a Danish family with autosomal dominant inherited dementia, a clinical phenotype resembling Alzheimer's disease and a pathogenic mutation (R406W) in the microtubule associated protein tau (MAPT) gene. Pre-symptomatic and affected family members underwent multidisciplinary (clinical, molecular, neuroimaging and neuropathological) examinations. Treatment with memantine in a family member with early symptoms, based on the clinical phenotype and the lack of specific treatment, appears to stabilize the disease course and increase the glucose metabolism in cortical and subcortical areas, as determined by serial [F(18)]FDG-PET scanning before and after initiation of treatment. Neuropathological examination of a second affected and mutation-positive family member showed moderate atrophy of the temporal lobes including the hippocampi. Microscopy revealed abundant numbers of tau-positive neurofibrillary tangles in all cortical areas and in some brainstem nuclei corresponding to a diagnosis of frontotemporal lobe degeneration on the basis of a MAPT mutation. The clinical and genetic heterogeneity of autosomal dominant inherited dementia must be taken into account in the genetic counselling and genetic testing of families with autosomal dominantly inherited dementia in general Udgivelsesdato: 2008/4",

author = "S.G. Lindquist and I.E. Holm and M. Schwartz and I. Law and J. Stokholm and M. Batbayli and Gunhild Waldemar and J.E. Nielsen",

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TY - JOUR

T1 - Alzheimer disease-like clinical phenotype in a family with FTDP-17 caused by a MAPT R406W mutation

AU - Lindquist, S.G.

AU - Holm, I.E.

AU - Schwartz, M.

AU - Law, I.

AU - Stokholm, J.

AU - Batbayli, M.

AU - Waldemar, Gunhild

AU - Nielsen, J.E.

PY - 2008

Y1 - 2008

N2 - We report clinical, molecular, neuroimaging and neuropathological features of a Danish family with autosomal dominant inherited dementia, a clinical phenotype resembling Alzheimer's disease and a pathogenic mutation (R406W) in the microtubule associated protein tau (MAPT) gene. Pre-symptomatic and affected family members underwent multidisciplinary (clinical, molecular, neuroimaging and neuropathological) examinations. Treatment with memantine in a family member with early symptoms, based on the clinical phenotype and the lack of specific treatment, appears to stabilize the disease course and increase the glucose metabolism in cortical and subcortical areas, as determined by serial [F(18)]FDG-PET scanning before and after initiation of treatment. Neuropathological examination of a second affected and mutation-positive family member showed moderate atrophy of the temporal lobes including the hippocampi. Microscopy revealed abundant numbers of tau-positive neurofibrillary tangles in all cortical areas and in some brainstem nuclei corresponding to a diagnosis of frontotemporal lobe degeneration on the basis of a MAPT mutation. The clinical and genetic heterogeneity of autosomal dominant inherited dementia must be taken into account in the genetic counselling and genetic testing of families with autosomal dominantly inherited dementia in general Udgivelsesdato: 2008/4

AB - We report clinical, molecular, neuroimaging and neuropathological features of a Danish family with autosomal dominant inherited dementia, a clinical phenotype resembling Alzheimer's disease and a pathogenic mutation (R406W) in the microtubule associated protein tau (MAPT) gene. Pre-symptomatic and affected family members underwent multidisciplinary (clinical, molecular, neuroimaging and neuropathological) examinations. Treatment with memantine in a family member with early symptoms, based on the clinical phenotype and the lack of specific treatment, appears to stabilize the disease course and increase the glucose metabolism in cortical and subcortical areas, as determined by serial [F(18)]FDG-PET scanning before and after initiation of treatment. Neuropathological examination of a second affected and mutation-positive family member showed moderate atrophy of the temporal lobes including the hippocampi. Microscopy revealed abundant numbers of tau-positive neurofibrillary tangles in all cortical areas and in some brainstem nuclei corresponding to a diagnosis of frontotemporal lobe degeneration on the basis of a MAPT mutation. The clinical and genetic heterogeneity of autosomal dominant inherited dementia must be taken into account in the genetic counselling and genetic testing of families with autosomal dominantly inherited dementia in general Udgivelsesdato: 2008/4

U2 - 10.1111/j.1468-1331.2008.02069.x

DO - 10.1111/j.1468-1331.2008.02069.x

M3 - Journal article

SN - 1351-5101

VL - 15

SP - 377

EP - 385

JO - European Journal of Neurology

JF - European Journal of Neurology

IS - 4

ER -