MAPT duplication (tissue request)

 
   Lead Investigator:    Magalie Lecourtois
   Institution      :    Institut de Recherche et d'Innovation Biom??dicale
   E-Mail           :    magalie.lecourtois@univ-rouen.fr
   Proposal ID      :    950



   Proposal Description:
   Our group recently described duplications of the 17q21.31 locus, encompassing  the MAPT gene, in patients with a clinical diagnosis of early-onset Alzheimer  disease (17q21.31 duplication causes prominent tau-related dementia with  increased MAPT expression. Le Guennec K et al, Mol Psychiatry. 2016 Dec 13.).  These patients have CSF biomarkers consistent with the diagnosis of AD, i.e.  decreased A??42 levels and increased Tau and P-Tau levels. However, amyloid PET  performed on 3 cases was negative, and routine neuropathological examination of  one case (by G Kovacs, Alexander et al Neurobiology of Aging, 2016) revealed a  pure tauopathy with abundant NFT pathology was seen in the hippocampus and  basal nucleus of Meynert, but without A?? deposits. We hypothesized that the  decreased CSF level of A??42 could be consistent with an increased level of A??  oligomers in the cerebral parenchyma, which are hardly detectable by amyloid  PET imaging or immunostaining.                                          We recently obtained a grant to further investigate the pathophysiological  mechanisms driven by this duplication.  Unfortunately, there is no frozen  tissue available for the patient with the neuropathological examination  described in our study. It is therefore essential for us to identify novel MAPT  duplication carriers.                                                   We are looking for  frozen embedded brain samples coming from individuals with  a clinical diagnosis of early-onset Alzheimer disease but presenting only tau  pathology at neuropathological examination.