ABSTRACT
Objective To explore the clinical and neuroimaging features of a frontotemporal dementia with parkinsonism linked to chromosome 17 ( FTDP-17 ) pedigree caused by mutation of microtubule-associated protein tau ( MAPT) gene.Methods The proband and one patient from a FTDP-17 pedigree were assessed through standardized clinical evaluation , neuropsychology assessment , video-electroencephalogrom ,MRI, genetic sequencing , as well as 18 F fludeoxyglucose ( FDG) SPECT for brain metabolism and 11 C 2β-carbomethoxy-3β-( 4-fluoro ) tropane ( CFT ) PET for dopamine transporter ( DAT ) distribution, respectively.Results A FTDP pedigree with 15 patients (6 still alive) was recruited to this study.The proband and one affected patient were genotyped and confirmed as MAPT c .1788T>G mutation. Parkinsonism was the first symptom for both two patients . Personality, speech changes and dementia accompanied with brain atrophy were developed at the later stage in one patient .The 18 F FDG SPECT studies illustrated asymmetric hypometabolism of the temporal , frontal lobes and basal ganglia in two patients . Regarding to the 11 C CFT PET, one affected patient showed asymmetric decreased uptake of tracer in basal ganglia regions.Conclusions FTDP-17 can display a confusingly broad clinical phenotype , with the parkinsonism as the first symptom . Brain glucose metabolism and DAT distribution could be potential biomarkers in early diagnosis of FTDP-17.
ABSTRACT
Objective To develop a model that could roundly show the phenotypes of human alzheimer disease (AD), the triple-transgenic rat model harboring APP(Swe), PS1dE9, and TAU transgenes was established in view of the advantage of rat as an important animal model on the research of nerve system .Methods APPswe/PS1dE9/TAU triple transgenic rat AD rats were generated on a SD background by co-injecting rat pronuclei with two human genes driven by the mouse prion promoter:‘Swedish’ mutant human APP (APPsw) and exon 9 mutant human presenilin-1 (PS1dE9) and human microtubule-associated protein tau gene under the control of PDGF promoter .Transgene integration was confirmed by genotyping and expression levels were evaluated by western blot ( WB ) of brain homogenates .The pathological changes were detected by human Abeta, TAU and Phospho-PHF-TAU immunohistochemistry staining (IHC).The behavioral and cognitive changes were evaluated by Morris water maze .Results One transgenic rat lines with high human APP ( Swe ) , PS1dE9, and TAU transgenic expression was selected from three transgenic founders .Compared with the wild type rat , the transgenic rat showed significant learning and memory impairments in the Morris water maze at 6 months of age .The triple transgenic rat manifested hyperphosphorylated tau and obvious aggregation of amyloid -β( Aβ) in the brain cortex and hippocampus.Conclusion APPswe/PS1dE9/TAU triple transgenic rat AD model was established .The triple transgenic AD rat fills a critical need for a next-generation animal model to enable basic and translational AD research .
ABSTRACT
@#Alzheimer's disease (AD) is the general neurodegenerative disease in the elderly. Alterations of microtubule associated protein tau are closely related to the onset and progression of AD. The role of tau protein in the development of AD has been a focus in the current study of AD, with an emphasis on the identification of compounds that inhibit tau protein phosphorylation and aggregate, and accelerate tau protein depolymerization. The current research status of tau protein as target of AD preventive and therapeutic drug was also reviewed.
ABSTRACT
Alzheimer's disease (AD) is the general neurodegenerative disease in the elderly. Alterations of microtubule associated pro-tein tau are closely related to the onset and progression of AD. The role of tau protein in the development of AD has been a focus in the cur-rent study of AD, with an emphasis on the identification of compounds that inhibit tau protein phosphorylation and aggregate, and accelerate tau protein depolymerization. The current research status of tau protein as target of AD preventive and therapeutic drug was also reviewed.