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.
authors.affiliation: Memory Disorders Research Group, The Neuroscience Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. granhojlindquist@gmail.com
authors.forename: S G
authors.initials: SG
authors.lastname: Lindquist
authors.forename: I E
authors.initials: IE
authors.lastname: Holm
authors.forename: M
authors.initials: M
authors.lastname: Schwartz
authors.forename: I
authors.initials: I
authors.lastname: Law
authors.forename: J
authors.initials: J
authors.lastname: Stokholm
authors.forename: M
authors.initials: M
authors.lastname: Batbayli
authors.forename: G
authors.initials: G
authors.lastname: Waldemar
authors.forename: J E
authors.initials: JE
authors.lastname: Nielsen
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001120:Arginine / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17; D003704:Dementia / Q000150:complications; D003718:Denmark; D003847:Deoxyglucose / Q000378:metabolism; D005192:Family Health; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016874:Neurofibrillary Tangles / Q000378:metabolism; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D010446:Peptide Fragments / Q000378:metabolism; D010641:Phenotype; D049268:Positron-Emission Tomography / Q000379:methods; D014364:Tryptophan / Q000235:genetics*; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D014364:Tryptophan; D001120:Arginine; D003847:Deoxyglucose