Tauopathies brain

Capatros-Lefebvre D, Seigeant N, Lees A, Camuzat A, Daniel S, Lannuzel A et al (2002) Guadeloupean parkinsonism a cluster of progressive supranuclear palsy-Uke tauopathy. Brain 125 801-811... 

Tau pathology in AD is circumscribed to neurons, while in other tauopathies, such as corticobasal degeneration, PSP and familial multiple system tauopathy with presenile dementia, both nerve cells and ghal cells are affected (210,211). PINl binds hyperphosphorylated tau, resulting in depletion of soluble PINl in AD brains. 

Mutations that stimulate exon 10 inclusion into the human tau mRNA, which is regulated by an intricate interplay of cis elements and trans factors, cause FTDP-17 and other tauopathies. This suggests that the ratio of exon 10 inclusion to exclusion in the adult brain is one of the factors to determine biological functions of the tau protein. 

Ramakrishnan P, Dickson DW, Davies P (2003) Pinl colocahzation with phosphorylated tau in Alzheimer s disease and other tauopathies. Neurobiol Dis 14 251-264 Rapoport SI (1999) In vivo PET imaging and postmortem studies suggest potentially reversible and irreversible stages of brain metabohc failure in Alzheimer s disease. Eur Arch Psychiatry CUn Neurosci 249(Suppl 3) 46-55... 

Snowden JS, Neary D, Mann DM (2002) Frontotemporal dementia. Br J Psychiatry 180 140-143 Sontag E, Nunbhakdi-Craig V, Lee G, Brandt R, Kamibayashi C, Kuret J, et al. (1999) Molecular interactions among protein phosphatase 2A, tau, and microtubules. Imphcations for the regulation of tau phosphorylation and the development of tauopathies. J Biol Chem 274 25490-25498 SpUlantini MG, Goedert M (2000) Tau mutations in familial frontotemporal dementia. Brain 123(Pt 5) 857-859... 

Plaques and tangles in the hippocampus and cortex are still considered the seminal findings in AD neuropathology, and conventional features to establish the boundary between amyloidopathies and tauopathies however, both phenotypic markers are also present in normal brains, in over 60 % of cases with traumatic brain injury, and in many other brain disorders [94-96],... 

The fink between GSK-3 and Alzheimer s disease is strongly supported by both pre-clinical in vivo models for tauopathy and locahsation in hrnnan Alzheimer s disease brain. Therefore, in initial cHnical trials it will be critical to test the concept of GSK-3 inhibition in Alzheimer s disease, first by assessing safety and tolerabihty, and later on efficacy in disease. 

Zhukareva V, Vogelsberg-Ragaglia V, Van Deerlin VM et al. (2001) Loss of brain tau defines novel sporadic and familial tauopathies with frontotemporal dementia. Atjtj VcMrof 49(2), 165-175. 

---