%0 Journal Article
%A Valentino, Rebecca R
%A Scotton, William J
%A Roemer, Shanu F
%A Lashley, Tammaryn
%A Heckman, Michael G
%A Shoai, Maryam
%A Martinez-Carrasco, Alejandro
%A Tamvaka, Nicole
%A Walton, Ronald L
%A Baker, Matthew C
%A Macpherson, Hannah L
%A Real, Raquel
%A Soto-Beasley, Alexandra I
%A Mok, Kin
%A Revesz, Tamas
%A Christopher, Elizabeth A
%A DeTure, Michael
%A Seeley, William W
%A Lee, Edward B
%A Frosch, Matthew P
%A Molina-Porcel, Laura
%A Gefen, Tamar
%A Redding-Ochoa, Javier
%A Ghetti, Bernardino
%A Robinson, Andrew C
%A Kobylecki, Christopher
%A Rowe, James B
%A Beach, Thomas G
%A Teich, Andrew F
%A Keith, Julia L
%A Bodi, Istvan
%A Halliday, Glenda M
%A Gearing, Marla
%A Arzberger, Thomas
%A Morris, Christopher M
%A White, Charles L
%A Mechawar, Naguib
%A Boluda, Susana
%A MacKenzie, Ian R
%A McLean, Catriona
%A Cykowski, Matthew D
%A Wang, Shih-Hsiu J
%A Graff, Caroline
%A Nagra, Rashed M
%A Kovacs, Gabor G
%A Giaccone, Giorgio
%A Neumann, Manuela
%A Ang, Lee-Cyn
%A Carvalho, Agostinho
%A Morris, Huw R
%A Rademakers, Rosa
%A Hardy, John A
%A Dickson, Dennis W
%A Rohrer, Jonathan D
%A Ross, Owen A
%T MAPT H2 haplotype and risk of Pick's disease in the Pick's disease International Consortium: a genetic association study.
%J The lancet
%V 23
%N 5
%@ 1474-4422
%C London
%I Lancet Publ. Group
%M DZNE-2024-00488
%P 487 - 499
%D 2024
%X Pick's disease is a rare and predominantly sporadic form of frontotemporal dementia that is classified as a primary tauopathy. Pick's disease is pathologically defined by the presence in the frontal and temporal lobes of Pick bodies, composed of hyperphosphorylated, three-repeat tau protein, encoded by the MAPT gene. MAPT has two distinct haplotypes, H1 and H2; the MAPT H1 haplotype is the major genetic risk factor for four-repeat tauopathies (eg, progressive supranuclear palsy and corticobasal degeneration), and the MAPT H2 haplotype is protective for these disorders. The primary aim of this study was to evaluate the association of MAPT H2 with Pick's disease risk, age at onset, and disease duration.In this genetic association study, we used data from the Pick's disease International Consortium, which we established to enable collection of data from individuals with pathologically confirmed Pick's disease worldwide. For this analysis, we collected brain samples from individuals with pathologically confirmed Pick's disease from 35 sites (brainbanks and hospitals) in North America, Europe, and Australia between Jan 1, 2020, and Jan 31, 2023. Neurologically healthy controls were recruited from the Mayo Clinic (FL, USA, or MN, USA between March 1, 1998, and Sept 1, 2019). For the primary analysis, individuals were directly genotyped for the MAPT H1-H2 haplotype-defining variant rs8070723. In a secondary analysis, we genotyped and constructed the six-variant-defined (rs1467967-rs242557-rs3785883-rs2471738-rs8070723-rs7521) MAPT H1 subhaplotypes. Associations of MAPT variants and MAPT haplotypes with Pick's disease risk, age at onset, and disease duration were examined using logistic and linear regression models; odds ratios (ORs) and β coefficients were estimated and correspond to each additional minor allele or each additional copy of the given haplotype.We obtained brain samples from 338 people with pathologically confirmed Pick's disease (205 [61
%K Female
%K Humans
%K Male
%K Genetic Association Studies
%K Haplotypes
%K Pick Disease of the Brain: genetics
%K tau Proteins: genetics
%K Tauopathies
%K MAPT protein, human (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:38631765
%R 10.1016/S1474-4422(24)00083-8
%U https://pub.dzne.de/record/269189