Additional file 1: Figure S1. of Slowly progressive dementia caused by MAPT R406W mutations: longitudinal report on a new kindred and systematic review

Additional neuropathology. Additional photomicrographs from three family members. Individuals, immunohistochemistry, and enlargement as indicated. (TIF 11179 kb

Additional file 4: Table S3. of Slowly progressive dementia caused by MAPT R406W mutations: longitudinal report on a new kindred and systematic review

Cerebrospinal fluid examinations. Numbers in parentheses indicate disease duration when cerebrospinal fluid was retrieved. Upward filled triangles = value above laboratory’s reference value for healthy individuals; downward filled triangles = value below laboratory’s reference value for healthy individuals. aCompared with healthy control subjects (157 ± 65 pg/ml, n = 24) and patients with AD (555 ± 248 pg/ml, n = 31). bCompared with healthy control subjects (29 ± 10 pg/ml, n = 21) and patients with AD (86 ± 39 pg/ml, n = 31). N/A Not assessed. (PDF 304 kb

Additional file 3: Table S2. of Slowly progressive dementia caused by MAPT R406W mutations: longitudinal report on a new kindred and systematic review

Individual data from previous publications (systematic review). Numbers indicate disease duration at first reported or observed symptom. Data in parentheses are successive or vaguely specified development or data unspecifically described. *Symptoms reported by patient or relative. #Unreliable data owing to possible pharmacological cause (neuroleptics). §Data too imprecisely reported to be included in calculations. AD Alzheimer’s disease, MCI Mild cognitive impairment, Dementia NOS Dementia not otherwise specified, CSF Cerebrospinal fluid, Aβ 42 Amyloid-β 1–42, APOE Apolipoprotein E, ADL Activities of daily living. (PDF 161 kb

Additional file 2: Table S1. of Slowly progressive dementia caused by MAPT R406W mutations: longitudinal report on a new kindred and systematic review

MAPT haplotype determination based on exome sequencing data. Individuals, residues, and haplotype as indicated. Note that the proband, individual III-2, had Alzheimer’s disease and was excluded from the study. (PDF 181 kb

Additional file 1: Figure S1. of Slowly progressive dementia caused by MAPT R406W mutations: longitudinal report on a new kindred and systematic review

Additional neuropathology. Additional photomicrographs from three family members. Individuals, immunohistochemistry, and enlargement as indicated. (TIF 11179 kb

Additional file 4: Table S2. of The PINK1 p.I368N mutation affects protein stability and ubiquitin kinase activity

FoldX measurement for mutational energy effect on stability of binding pocket. Using the FoldX algorithm, which compares the WT structure with the mutant, calculations on WT and mutant at t = 0 and after 100 ns were performed. While WT is nearly zero over that time interval, the N368 mutant increases energy (∆∆G) by 1.5–2 kcal/mol*Å2. This modest increase supports that the mutation distorts the local region via an increase of Gibb’s free energy. (DOCX 16 kb

Additional file 5: Figure S1. of The PINK1 p.I368N mutation affects protein stability and ubiquitin kinase activity

Reduced full-length PINK1 levels in p.I368N mutant fibroblasts upon treatment with valinomycin. (A) Representative confocal IF images of control and two PINK1 p.I368N fibroblasts showing mitochondrial localization but greatly reduced levels of the mutant protein. Cells were left untreated (-) or treated with 10 μM CCCP for 6 days (+) and stained with antibodies against PINK1 (green) and TOM20 (mitochondria, red). Nuclei were counterstained with Hoechst (blue). Scale bars represent 10 μm. (B) Subcellular fractionation of WT control and PINK1 p.I368N fibroblasts treated with or without 1 μM valinomycin for 24 h. Despite different protein levels, both WT and p.I368N mutant full-length PINK1 localized to the mitochondrial fraction. A shift of PARKIN into higher molecular weights species indicative of PINK1-dependent activation was not observed in lysates from PINK1 p.I368N mutant cells. Purity of the mitochondrial and cytosolic fractions was determined using antibodies recognizing TOM20 and p38 MAPK, respectively. PNS denotes post-nuclear supernatant. (C) Control and two PINK1 p.I368N fibroblasts were treated with 1 μM valinomycin for 0, 2, 4 or 8 h and total lysates were analyzed by WB with indicated antibodies. GAPDH served as a loading control. Similar to CCCP treatment (Fig. 3b), rapid stabilization of full-length PINK1 along with an increase of p-Ser65-Ub levels was observed in control cells, but not in PINK1 p.I368N mutant fibroblasts. (D) Representative Images obtained with a 20x magnification on the BD pathway 855 system. Control fibroblasts and PINK1 I368N cells were seeded in 96-well imaging plates and treated with valinomycin as indicated. Cells were fixed and stained with p-S65-Ub antibodies (green) and Hoechst (blue). Scale bars indicate 10 μm. (TIF 13839 kb

Additional file 1: of Replication of progressive supranuclear palsy genome-wide association study identifies SLCO1A2 and DUSP10 as new susceptibility loci

Figure S1. SLCO1A2 rs11568563 GWAS signal set. LD Manhattan plot for rs11568563 in the 1000G phase3:CEU as visualized using Ensembl (A). Genomic location of genes neighboring rs11568563 GWAS signal set as visualized in UCSC Genome Browser (B) with customized tracks from top to bottom: R2 plot for rs11568563, proxy variants in strong LD (r2 > 0.8) with rs11568563, USCS genes found to have differential brain expression and their associated GTEx RNA-seq gene expression (brain expression in yellow). (TIF 2794 kb