Neuroscience 2005 Abstract
| Presentation Number: | 360.9 |
|---|---|
| Abstract Title: | Characterization of tau in human frontal cortex on a neuropathological cohort of tauopathies. |
| Authors: |
Ingelsson, M.*1,2
; Russ, C.2
; Ramasamy, K.2
; Orne, J.2
; Skoglund, L.1
; Raju, S.2
; Growdon, J. H.2
; Frosch, M. P.2
; Ghetti, B.3
; Brown Jr., R. H.2
; Irizarry, M. C.2
; Hyman, B. T.2
1Public Health/Geriatrics, Uppsala Univ., Uppsala, Sweden 2MA, Molekylär Geriatrik, Rudbecklaboratoriet, Dag Hammarskjölds väg 20, 751 85, 3USA, Molekylär Geriatrik, Rudbecklaboratoriet, Dag Hammarskjölds väg 20, 751 85, |
| Primary Theme and Topics |
Disorders of the Nervous System - Neurodegenerative and Movement Disorders -- Dementia: Tau |
| Session: |
360. Tau and Tau Kinases III Slide |
| Presentation Time: | Monday, November 14, 2005 10:00 AM-10:15 AM |
| Location: | Washington Convention Center - Room 152A |
| Keywords: | neurodegeneration, alternative splicing, RNA, protein |
Familial frontotemporal dementia (FTD) can be caused by mutations in the tau gene on chromosome 17 (FTDP 17). One of the proposed mechanisms for tau mutations is a shift in expression of 4R tau vs. 3R tau. In progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), there is mainly 4R tau brain pathology.
We examined the prevalence of tau mutations and levels of tau protein and 4R tau/3R tau mRNA in frontal cortex from brains of the Massachusetts Alzheimer’s Disease Research Center, representing 17 FTD, 21 PSP, 5 CBD, 15 Alzheimer’s disease (AD) and 16 control cases.
Two tau gene mutations were found among the FTD brains. One case carried the P301L mutation and one had a new tau mutation, V248L. Total tau protein levels, by ELISA, were decreased among FTD (63 µg/g) and AD (67 µg/g) cases as compared to controls (80 µg/g). Total tau mRNA levels, by quantitative PCR, were lower in FTD (537 x 103 molecules/µg cDNA) and PSP (550 x 103 molecules/µg cDNA) than in controls (992 x 103 molecules/µg cDNA). The ratio of 4R tau/3R tau mRNA was higher in FTD (1.32) and PSP (1.12) than in controls (0.48). Interestingly, there was a substantial variation in the 4R tau/3R tau ratio within the FTD and PSP groups and some apparently sporadic FTD and PSP cases had higher 4R tau/3R tau mRNA ratios than four FTDP17 cases with tau mutations that were included as reference tissues.
In summary, we have found a novel disease-causing tau mutation, V248L. The decrease in tau protein or mRNA levels in the frontal cortex of FTD, AD, and PSP likely reflects neuronal loss in this area. The substantial variation in 4R tau/3R tau mRNA ratios in FTD and PSP suggests heterogeneous pathophysiological processes within these diagnoses.
We examined the prevalence of tau mutations and levels of tau protein and 4R tau/3R tau mRNA in frontal cortex from brains of the Massachusetts Alzheimer’s Disease Research Center, representing 17 FTD, 21 PSP, 5 CBD, 15 Alzheimer’s disease (AD) and 16 control cases.
Two tau gene mutations were found among the FTD brains. One case carried the P301L mutation and one had a new tau mutation, V248L. Total tau protein levels, by ELISA, were decreased among FTD (63 µg/g) and AD (67 µg/g) cases as compared to controls (80 µg/g). Total tau mRNA levels, by quantitative PCR, were lower in FTD (537 x 103 molecules/µg cDNA) and PSP (550 x 103 molecules/µg cDNA) than in controls (992 x 103 molecules/µg cDNA). The ratio of 4R tau/3R tau mRNA was higher in FTD (1.32) and PSP (1.12) than in controls (0.48). Interestingly, there was a substantial variation in the 4R tau/3R tau ratio within the FTD and PSP groups and some apparently sporadic FTD and PSP cases had higher 4R tau/3R tau mRNA ratios than four FTDP17 cases with tau mutations that were included as reference tissues.
In summary, we have found a novel disease-causing tau mutation, V248L. The decrease in tau protein or mRNA levels in the frontal cortex of FTD, AD, and PSP likely reflects neuronal loss in this area. The substantial variation in 4R tau/3R tau mRNA ratios in FTD and PSP suggests heterogeneous pathophysiological processes within these diagnoses.
Supported by NIH (P50 AG005134), the Swedish Research Council and the Angel Fund.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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