Inhibitory Roles of Apolipoprotein E Christchurch Astrocytes in Curbing Tau Propagation Using Human Pluripotent Stem Cell-Derived Models
Murakami R, Watanabe H, Hashimoto H, Kashiwagi-Hakozaki M, Hashimoto T, Karch CM, Iwatsubo T, Okano H. Inhibitory Roles of Apolipoprotein E Christchurch Astrocytes in Curbing Tau Propagation Using Human Pluripotent Stem Cell-Derived Models. J Neurosci. 2024 Jun 12;44(24). doi: 10.1523/JNEUROSCI.1709-23.2024. PubMed PMID: 38649269; PubMed Central PMCID: PMC11170944.
α-Synuclein seed amplification assay detects Lewy body co-pathology in autosomal dominant Alzheimer’s disease late in the disease course and dependent on Lewy pathology burden
Levin J, Baiardi S, Quadalti C, Rossi M, Mammana A, Vöglein J, Bernhardt A, Perrin RJ, Jucker M, Preische O, Hofmann A, Höglinger GU, Cairns NJ, Franklin EE, Chrem P, Cruchaga C, Berman SB, Chhatwal JP, Daniels A, Day GS, Ryan NS, Goate AM, Gordon BA, Huey ED, Ibanez L, Karch CM, Lee JH, Llibre-Guerra J, Lopera F, Masters CL, Morris JC, Noble JM, Renton AE, Roh JH, Frosch MP, Keene CD, McLean C, Sanchez-Valle R, Schofield PR, Supnet-Bell C, Xiong C, Giese A, Hansson O, Bateman RJ, McDade E, Parchi P. α-Synuclein seed amplification assay detects Lewy body co-pathology in autosomal dominant Alzheimer’s disease late in the disease course and dependent on Lewy pathology burden. Alzheimers Dement. 2024 Jun;20(6):4351-4365. doi: 10.1002/alz.13818. Epub 2024 Apr 26. PubMed PMID: 38666355; PubMed Central PMCID: PMC11180868.
Cell autonomous microglia defects in a stem cell model of frontotemporal dementia
Iyer AK, Vermunt L, Mirfakhar FS, Minaya M, Acquarone M, Koppisetti RK, Renganathan A, You SF, Danhash EP, Verbeck A, Galasso G, Lee SM, Marsh J, Nana AL, Spina S, Seeley WW, Grinberg LT, Temple S, Teunissen CE, Sato C, Karch CM. Cell autonomous microglia defects in a stem cell model of frontotemporal dementia. medRxiv. 2024 May 16;. doi: 10.1101/2024.05.15.24307444. PubMed PMID: 38798451; PubMed Central PMCID: PMC11118656.
Comparison of tau spread in people with Down syndrome versus autosomal-dominant Alzheimer’s disease: a cross-sectional study
Wisch JK, McKay NS, Boerwinkle AH, Kennedy J, Flores S, Handen BL, Christian BT, Head E, Mapstone M, Rafii MS, O’Bryant SE, Price JC, Laymon CM, Krinsky-McHale SJ, Lai F, Rosas HD, Hartley SL, Zaman S, Lott IT, Tudorascu D, Zammit M, Brickman AM, Lee JH, Bird TD, Cohen A, Chrem P, Daniels A, Chhatwal JP, Cruchaga C, Ibanez L, Jucker M, Karch CM, Day GS, Lee JH, Levin J, Llibre-Guerra J, Li Y, Lopera F, Roh JH, Ringman JM, Supnet-Bell C, van Dyck CH, Xiong C, Wang G, Morris JC, McDade E, Bateman RJ, Benzinger TLS, Gordon BA, Ances BM. Comparison of tau spread in people with Down syndrome versus autosomal-dominant Alzheimer’s disease: a cross-sectional study. Lancet Neurol. 2024 May;23(5):500-510. doi: 10.1016/S1474-4422(24)00084-X. PubMed PMID: 38631766; PubMed Central PMCID: PMC11209765.
Brain high-throughput multi-omics data reveal molecular heterogeneity in Alzheimer’s disease
Eteleeb AM, Novotny BC, Tarraga CS, Sohn C, Dhungel E, Brase L, Nallapu A, Buss J, Farias F, Bergmann K, Bradley J, Norton J, Gentsch J, Wang F, Davis AA, Morris JC, Karch CM, Perrin RJ, Benitez BA, Harari O. Brain high-throughput multi-omics data reveal molecular heterogeneity in Alzheimer’s disease. PLoS Biol. 2024 Apr;22(4):e3002607. doi: 10.1371/journal.pbio.3002607. eCollection 2024 Apr. PubMed PMID: 38687811; PubMed Central PMCID: PMC11086901.
Novel avenues of tau research
Sexton CE, Bitan G, Bowles KR, Brys M, Buée L, Maina MB, Clelland CD, Cohen AD, Crary JF, Dage JL, Diaz K, Frost B, Gan L, Goate AM, Golbe LI, Hansson O, Karch CM, Kolb HC, La Joie R, Lee SE, Matallana D, Miller BL, Onyike CU, Quiroz YT, Rexach JE, Rohrer JD, Rommel A, Sadri-Vakili G, Schindler SE, Schneider JA, Sperling RA, Teunissen CE, Weninger SC, Worley SL, Zheng H, Carrillo MC. Novel avenues of tau research. Alzheimers Dement. 2024 Mar;20(3):2240-2261. doi: 10.1002/alz.13533. Epub 2024 Jan 3. Review. PubMed PMID: 38170841; PubMed Central PMCID: PMC10984447.
Vascularized Brain Assembloids With Enhanced Cellular Complexity Provide Insights Into the Cellular Deficits of Tauopathy
Sun X, Kofman S, Ogbolu VC, Karch CM, Ibric L, Qiang L. Vascularized Brain Assembloids With Enhanced Cellular Complexity Provide Insights Into the Cellular Deficits of Tauopathy. Stem Cells. 2024 Feb 8;42(2):107-115. doi: 10.1093/stmcls/sxad086. PubMed PMID: 37995336; PubMed Central PMCID: PMC10852025.
m6A-dependent circular RNA formation mediates tau-induced neurotoxicity
Atrian F, Ramirez P, De Mange J, Marquez M, Gonzalez EM, Minaya M, Karch CM, Frost B. m6A-dependent circular RNA formation mediates tau-induced neurotoxicity. bioRxiv. 2024 Jan 26;. doi: 10.1101/2024.01.25.577211. PubMed PMID: 38328044; PubMed Central PMCID: PMC10849734.
Etiology of White Matter Hyperintensities in Autosomal Dominant and Sporadic Alzheimer Disease
Shirzadi Z, Schultz SA, Yau WW, Joseph-Mathurin N, Fitzpatrick CD, Levin R, Kantarci K, Preboske GM, Jack CR Jr, Farlow MR, Hassenstab J, Jucker M, Morris JC, Xiong C, Karch CM, Levey AI, Gordon BA, Schofield PR, Salloway SP, Perrin RJ, McDade E, Levin J, Cruchaga C, Allegri RF, Fox NC, Goate A, Day GS, Koeppe R, Chui HC, Berman S, Mori H, Sanchez-Valle R, Lee JH, Rosa-Neto P, Ruthirakuhan M, Wu CY, Swardfager W, Benzinger TLS, Sohrabi HR, Martins RN, Bateman RJ, Johnson KA, Sperling RA, Greenberg SM, Schultz AP, Chhatwal JP. Etiology of White Matter Hyperintensities in Autosomal Dominant and Sporadic Alzheimer Disease. JAMA Neurol. 2023 Dec 1;80(12):1353-1363. doi: 10.1001/jamaneurol.2023.3618. PubMed PMID: 37843849; PubMed Central PMCID: PMC10580156.
Targeted ASO-mediated Atp1a2 knockdown in astrocytes reduces SOD1 aggregation and accelerates disease onset in mutant SOD1 mice
ct Iyer AK, Schoch KM, Verbeck A, Galasso G, Chen H, Smith S, Oldenborg A, Miller TM, Karch CM, Bonni A. Targeted ASO-mediated Atp1a2 knockdown in astrocytes reduces SOD1 aggregation and accelerates disease onset in mutant SOD1 mice. PLoS One. 2023;18(11):e0294731. doi: 10.1371/journal.pone.0294731. eCollection 2023. PubMed PMID: 38015828; PubMed Central PMCID: PMC10683999.
Mutant tau and stress lead to downregulation of long noncoding RNA, SNHG8
Bhagat R, Minaya MA, Renganathan A, Mehra M, Marsh J, Martinez R, Eteleeb AM, Nana AL, Spina S, Seeley WW, Grinberg LT, Karch CM. Mutant tau and stress lead to downregulation of long noncoding RNA, SNHG8. Mol Psychiatry. 2023 Nov;28(11):4489. doi: 10.1038/s41380-023-02328-0. PubMed PMID: 38443679; PubMed Central PMCID: PMC11197879.
Improved Protocol for Reproducible Human Cortical Organoids Reveals Early Alterations in Metabolism with MAPT Mutations
Bertucci T, Bowles KR, Lotz S, Qi L, Stevens K, Goderie SK, Borden S, Oja LM, Lane K, Lotz R, Lotz H, Chowdhury R, Joy S, Arduini BL, Butler DC, Miller M, Baron H, Sandhof CA, Silva MC, Haggarty SJ, Karch CM, Geschwind DH, Goate AM, Temple S. Improved Protocol for Reproducible Human Cortical Organoids Reveals Early Alterations in Metabolism with MAPT Mutations. bioRxiv. 2023 Jul 11;. doi: 10.1101/2023.07.11.548571. PubMed PMID: 37503195; PubMed Central PMCID: PMC10369860.
Endogenous recapitulation of Alzheimer’s disease neuropathology through human 3D direct neuronal reprogramming
Sun Z, Kwon JS, Ren Y, Chen S, Cates K, Lu X, Walker CK, Karahan H, Sviben S, Fitzpatrick JAJ, Valdez C, Houlden H, Karch CM, Bateman RJ, Sato C, Mennerick SJ, Diamond MI, Kim J, Tanzi RE, Holtzman DM, Yoo AS. Endogenous recapitulation of Alzheimer’s disease neuropathology through human 3D direct neuronal reprogramming. bioRxiv. 2023 May 25;. doi: 10.1101/2023.05.24.542155. PubMed PMID: 37292658; PubMed Central PMCID: PMC10245934.
Axonal damage and astrocytosis are biological correlates of grey matter network integrity loss: a cohort study in autosomal dominant Alzheimer disease
Vermunt L, Sutphen C, Dicks E, de Leeuw DM, Allegri R, Berman SB, Cash DM, Chhatwal JP, Cruchaga C, Day G, Ewers M, Farlow M, Fox NC, Ghetti B, Graff-Radford N, Hassenstab J, Jucker M, Karch CM, Kuhle J, Laske C, Levin J, Masters CL, McDade E, Mori H, Morris JC, Perrin RJ, Preische O, Schofield PR, Suárez-Calvet M, Xiong C, Scheltens P, Teunissen CE, Visser PJ, Bateman RJ, Benzinger TLS, Fagan AM, Gordon BA, Tijms BM. Axonal damage and astrocytosis are biological correlates of grey matter network integrity loss: a cohort study in autosomal dominant Alzheimer disease. medRxiv. 2023 Mar 22;. doi: 10.1101/2023.03.21.23287468. PubMed PMID: 37016671; PubMed Central PMCID: PMC10071836.
MS4A4A modifies the risk of Alzheimer disease by regulating lipid metabolism and immune response in a unique microglia state
You SF, Brase L, Filipello F, Iyer AK, Del-Aguila J, He J, D’Oliveira Albanus R, Budde J, Norton J, Gentsch J, Dräger NM, Sattler SM, Kampmann M, Piccio L, Morris JC, Perrin RJ, McDade E, Paul SM, Cashikar AG, Benitez BA, Harari O, Karch CM. MS4A4A modifies the risk of Alzheimer disease by regulating lipid metabolism and immune response in a unique microglia state. medRxiv. 2023 Feb 8;. doi: 10.1101/2023.02.06.23285545. PubMed PMID: 36798226; PubMed Central PMCID: PMC9934804.
ER-mitochondria contacts and cholesterol metabolism are disrupted by disease-associated tau protein
Szabo L, Cummins N, Paganetti P, Odermatt A, Papassotiropoulos A, Karch C, Götz J, Eckert A, Grimm A. ER-mitochondria contacts and cholesterol metabolism are disrupted by disease-associated tau protein. EMBO Rep. 2023 Aug 3;24(8):e57499. doi: 10.15252/embr.202357499. Epub 2023 Jul 4. PMID: 37401859; PMCID: PMC10398652.
Proteomics of brain, CSF, and plasma identifies molecular signatures for distinguishing sporadic and genetic Alzheimer’s disease
Sung YJ, Yang C, Norton J, Johnson M, Fagan A, Bateman RJ, Perrin RJ, Morris JC, Farlow MR, Chhatwal JP, Schofield PR, Chui H, Wang F, Novotny B, Eteleeb A, Karch C, Schindler SE, Rhinn H, Johnson ECB, Oh HS, Rutledge JE, Dammer EB, Seyfried NT, Wyss-Coray T, Harari O, Cruchaga C. Proteomics of brain, CSF, and plasma identifies molecular signatures for distinguishing sporadic and genetic Alzheimer’s disease. Sci Transl Med. 2023 Jul 5;15(703):eabq5923. doi: 10.1126/scitranslmed.abq5923. Epub 2023 Jul 5. PMID: 37406134.
Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer’s disease
Johnson ECB, Bian S, Haque RU, Carter EK, Watson CM, Gordon BA, Ping L, Duong DM, Epstein MP, McDade E, Barthélemy NR, Karch CM, Xiong C, Cruchaga C, Perrin RJ, Wingo AP, Wingo TS, Chhatwal JP, Day GS, Noble JM, Berman SB, Martins R, Graff-Radford NR, Schofield PR, Ikeuchi T, Mori H, Levin J, Farlow M, Lah JJ, Haass C, Jucker M, Morris JC, Benzinger TLS, Roberts BR, Bateman RJ, Fagan AM, Seyfried NT, Levey AI; Dominantly Inherited Alzheimer Network. Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer’s disease. Nat Med. 2023 Aug;29(8):1979-1988. doi: 10.1038/s41591-023-02476-4. Epub 2023 Aug 7. PMID: 37550416; PMCID: PMC10427428.
Positron emission tomography and magnetic resonance imaging methods and datasets within the Dominantly Inherited Alzheimer Network (DIAN)
McKay NS, Gordon BA, Hornbeck RC, Dincer A, Flores S, Keefe SJ, Joseph-Mathurin N, Jack CR, Koeppe R, Millar PR, Ances BM, Chen CD, Daniels A, Hobbs DA, Jackson K, Koudelis D, Massoumzadeh P, McCullough A, Nickels ML, Rahmani F, Swisher L, Wang Q, Allegri RF, Berman SB, Brickman AM, Brooks WS, Cash DM, Chhatwal JP, Day GS, Farlow MR, la Fougère C, Fox NC, Fulham M, Ghetti B, Graff-Radford N, Ikeuchi T, Klunk W, Lee JH, Levin J, Martins R, Masters CL, McConathy J, Mori H, Noble JM, Reischl G, Rowe C, Salloway S, Sanchez-Valle R, Schofield PR, Shimada H, Shoji M, Su Y, Suzuki K, Vöglein J, Yakushev I, Cruchaga C, Hassenstab J, Karch C, McDade E, Perrin RJ, Xiong C, Morris JC, Bateman RJ, Benzinger TLS; Dominantly Inherited Alzheimer Network. Positron emission tomography and magnetic resonance imaging methods and datasets within the Dominantly Inherited Alzheimer Network (DIAN). Nat Neurosci. 2023 Aug;26(8):1449-1460. doi: 10.1038/s41593-023-01359-8. Epub 2023 Jul 10. PMID: 37429916; PMCID: PMC10400428.
Location of pathogenic variants in PSEN1 impacts progression of cognitive, clinical, and neurodegenerative measures in autosomal-dominant Alzheimer’s disease
Schultz SA, Shirzadi Z, Schultz AP, Liu L, Fitzpatrick CD, McDade E, Barthelemy NR, Renton A, Esposito B, Joseph-Mathurin N, Cruchaga C, Chen CD, Goate A, Allegri RF, Benzinger TLS, Berman S, Chui HC, Fagan AM, Farlow MR, Fox NC, Gordon BA, Day GS, Graff-Radford NR, Hassenstab JJ, Hanseeuw BJ, Hofmann A, Jack CR Jr, Jucker M, Karch CM, Koeppe RA, Lee JH, Levey AI, Levin J, Martins RN, Mori H, Morris JC, Noble J, Perrin RJ, Rosa-Neto P, Salloway SP, Sanchez-Valle R, Schofield PR, Xiong C, Johnson KA, Bateman RJ, Sperling RA, Chhatwal JP; Dominantly Inherited Alzheimer Network Investigators. Location of pathogenic variants in PSEN1 impacts progression of cognitive, clinical, and neurodegenerative measures in autosomal-dominant Alzheimer’s disease. Aging Cell. 2023 Aug;22(8):e13871. doi: 10.1111/acel.13871. Epub 2023 Jun 8. PMID: 37291760; PMCID: PMC10410059.