Discovery and validation of dominantly inherited Alzheimer’s disease mutations in populations from Latin America
Takada LT, Aláez-Verson C, Burgute BD, Nitrini R, Sosa AL, Castilhos RM, Chaves MF, Longoria EM, Carrillo-Sánchez K, Brucki SMD, Flores-Lagunes LL, Molina C, Olivares MJ, Ziegemeier E, Petranek J, Goate AM, Cruchaga C, Renton AE, Fernández MV, Day GS, McDade E, Bateman RJ, Karch CM, Llibre-Guerra JJ; Dominantly Inherited Alzheimer Network. Discovery and validation of dominantly inherited Alzheimer’s disease mutations in populations from Latin America. Alzheimers Res Ther. 2022 Aug 5;14(1):108. doi: 10.1186/s13195-022-01052-1. PMID: 35932032; PMCID: PMC9354296.
Cholesterol and matrisome pathways dysregulated in astrocytes and microglia
Tcw J, Qian L, Pipalia NH, Chao MJ, Liang SA, Shi Y, Jain BR, Bertelsen SE, Kapoor M, Marcora E, Sikora E, Andrews EJ, Martini AC, Karch CM, Head E, Holtzman DM, Zhang B, Wang M, Maxfield FR, Poon WW, Goate AM. Cholesterol and matrisome pathways dysregulated in astrocytes and microglia. Cell. 2022 Jun 23;185(13):2213-2233.e25. doi: 10.1016/j.cell.2022.05.017. PMID: 35750033; PMCID: PMC9340815.
CSF Tau phosphorylation at Thr205 is associated with loss of white matter integrity in autosomal dominant Alzheimer disease
Strain JF, Barthelemy N, Horie K, Gordon BA, Kilgore C, Aschenbrenner A, Cruchaga C, Xiong C, Joseph-Mathurin N, Hassenstab J, Fagan AM, Li Y, Karch CM, Perrin RJ, Berman SB, Chhatwal JP, Graff-Radford NR, Mori H, Levin J, Noble JM, Allegri R, Schofield PR, Marcus DS, Holtzman DM, Morris JC, Benzinger TLS, McDade EM, Bateman RJ, Ances BM. CSF Tau phosphorylation at Thr205 is associated with loss of white matter integrity in autosomal dominant Alzheimer disease. Neurobiol Dis. 2022 Jun 15;168:105714. doi: 10.1016/j.nbd.2022.105714. Epub 2022 Mar 28. PMID: 35358703; PMCID: PMC9701560.
Recapitulation of endogenous 4R tau expression and formation of insoluble tau in directly reprogrammed human neurons
Capano LS, Sato C, Ficulle E, Yu A, Horie K, Kwon JS, Burbach KF, Barthélemy NR, Fox SG, Karch CM, Bateman RJ, Houlden H, Morimoto RI, Holtzman DM, Duff KE, Yoo AS. Recapitulation of endogenous 4R tau expression and formation of insoluble tau in directly reprogrammed human neurons. Cell Stem Cell. 2022 Jun 2;29(6):918-932.e8. doi: 10.1016/j.stem.2022.04.018. PMID: 35659876; PMCID: PMC9176216.
Pattern and implications of neurological examination findings in autosomal dominant Alzheimer disease
Vöglein J, Franzmeier N, Morris JC, Dieterich M, McDade E, Simons M, Preische O, Hofmann A, Hassenstab J, Benzinger TL, Fagan A, Noble JM, Berman SB, Graff-Radford NR, Ghetti B, Farlow MR, Chhatwal JP, Salloway S, Xiong C, Karch CM, Cairns N, Perrin RJ, Day G, Martins R, Sanchez-Valle R, Mori H, Shimada H, Ikeuchi T, Suzuki K, Schofield PR, Masters CL, Goate A, Buckles V, Fox NC, Chrem P, Allegri R, Ringman JM, Yakushev I, Laske C, Jucker M, Höglinger G, Bateman RJ, Danek A, Levin J; Dominantly Inherited Alzheimer Network. Pattern and implications of neurological examination findings in autosomal dominant Alzheimer disease. Alzheimers Dement. 2023 Feb;19(2):632-645. doi: 10.1002/alz.12684. Epub 2022 May 24. PMID: 35609137; PMCID: PMC9684350.
Biomarker clustering in autosomal dominant Alzheimer’s disease
Luckett PH, Chen C, Gordon BA, Wisch J, Berman SB, Chhatwal JP, Cruchaga C, Fagan AM, Farlow MR, Fox NC, Jucker M, Levin J, Masters CL, Mori H, Noble JM, Salloway S, Schofield PR, Brickman AM, Brooks WS, Cash DM, Fulham MJ, Ghetti B, Jack CR Jr, Vöglein J, Klunk WE, Koeppe R, Su Y, Weiner M, Wang Q, Marcus D, Koudelis D, Joseph-Mathurin N, Cash L, Hornbeck R, Xiong C, Perrin RJ, Karch CM, Hassenstab J, McDade E, Morris JC, Benzinger TLS, Bateman RJ, Ances BM; Dominantly Inherited Alzheimer Network (DIAN). Biomarker clustering in autosomal dominant Alzheimer’s disease. Alzheimers Dement. 2023 Jan;19(1):274-284. doi: 10.1002/alz.12661. Epub 2022 Apr 1. PMID: 35362200; PMCID: PMC9525451.
Soluble TREM2 in CSF and its association with other biomarkers and cognition in autosomal-dominant Alzheimer’s disease: a longitudinal observational study
Morenas-Rodríguez E, Li Y, Nuscher B, Franzmeier N, Xiong C, Suárez-Calvet M, Fagan AM, Schultz S, Gordon BA, Benzinger TLS, Hassenstab J, McDade E, Feederle R, Karch CM, Schlepckow K, Morris JC, Kleinberger G, Nellgard B, Vöglein J, Blennow K, Zetterberg H, Ewers M, Jucker M, Levin J, Bateman RJ, Haass C; Dominantly Inherited Alzheimer Network. Soluble TREM2 in CSF and its association with other biomarkers and cognition in autosomal-dominant Alzheimer’s disease: a longitudinal observational study. Lancet Neurol. 2022 Apr;21(4):329-341. doi: 10.1016/S1474-4422(22)00027-8. Erratum in: Lancet Neurol. 2022 May;21(5):e5. PMID: 35305339; PMCID: PMC8926925.
Identification of the Aβ37/42 peptide ratio in CSF as an improved Aβ biomarker for Alzheimer’s disease
Liu L, Lauro BM, He A, Lee H, Bhattarai S, Wolfe MS, Bennett DA, Karch CM, Young-Pearse T; Dominantly Inherited Alzheimer Network (DIAN); Selkoe DJ. Identification of the Aβ37/42 peptide ratio in CSF as an improved Aβ biomarker for Alzheimer’s disease. Alzheimers Dement. 2023 Jan;19(1):79-96. doi: 10.1002/alz.12646. Epub 2022 Mar 12. PMID: 35278341; PMCID: PMC9464800.
Astrocytic α2-Na+/K+ ATPase inhibition suppresses astrocyte reactivity and reduces neurodegeneration in a tauopathy mouse model
Mann CN, Devi SS, Kersting CT, Bleem AV, Karch CM, Holtzman DM, Gallardo G. Astrocytic α2-Na+/K+ ATPase inhibition suppresses astrocyte reactivity and reduces neurodegeneration in a tauopathy mouse model. Sci Transl Med. 2022 Feb 16;14(632):eabm4107. doi: 10.1126/scitranslmed.abm4107. Epub 2022 Feb 16. PMID: 35171651; PMCID: PMC9161722.
Variant-dependent heterogeneity in amyloid β burden in autosomal dominant Alzheimer’s disease: cross-sectional and longitudinal analyses of an observational study
Chhatwal JP, Schultz SA, McDade E, Schultz AP, Liu L, Hanseeuw BJ, Joseph-Mathurin N, Feldman R, Fitzpatrick CD, Sparks KP, Levin J, Berman SB, Renton AE, Esposito BT, Fernandez MV, Sung YJ, Lee JH, Klunk WE, Hofmann A, Noble JM, Graff-Radford N, Mori H, Salloway SM, Masters CL, Martins R, Karch CM, Xiong C, Cruchaga C, Perrin RJ, Gordon BA, Benzinger TLS, Fox NC, Schofield PR, Fagan AM, Goate AM, Morris JC, Bateman RJ, Johnson KA, Sperling RA; Dominantly Inherited Alzheimer’s Network Investigators. Variant-dependent heterogeneity in amyloid β burden in autosomal dominant Alzheimer’s disease: cross-sectional and longitudinal analyses of an observational study. Lancet Neurol. 2022 Feb;21(2):140-152. doi: 10.1016/S1474-4422(21)00375-6. PMID: 35065037.
Soluble TREM2: Innocent bystander or active player in neurological diseases?
Filipello F, Goldsbury C, You SF, Locca A, Karch CM, Piccio L. Soluble TREM2: Innocent bystander or active player in neurological diseases? Neurobiol Dis. 2022 Jan 15;165:105630. doi: 10.1016/j.nbd.2022.105630. Epub ahead of print. PMID: 35041990.
Astrocytic 4R tau expression drives astrocyte reactivity and dysfunction
Ezerskiy LA, Schoch KM, Sato C, Beltcheva M, Horie K, Rigo F, Martynowicz R, Karch CM, Bateman RJ, Miller TM. Astrocytic 4R tau expression drives astrocyte reactivity and dysfunction. JCI Insight. 2022 Jan 11;7(1):e152012. doi: 10.1172/jci.insight.152012. PMID: 34874917; PMCID: PMC8765054.
Human brain organoids assemble functionally integrated bilateral optic vesicles
Gabriel E, Albanna W, Pasquini G, Ramani A, Josipovic N, Mariappan A, Schinzel F, Karch CM, Bao G, Gottardo M, Suren AA, Hescheler J, Nagel-Wolfrum K, Persico V, Rizzoli SO, Altmüller J, Riparbelli MG, Callaini G, Goureau O, Papantonis A, Busskamp V, Schneider T, Gopalakrishnan J. Human brain organoids assemble functionally integrated bilateral optic vesicles. Cell Stem Cell. 2021 Oct 7;28(10):1740-1757.e8. doi: 10.1016/j.stem.2021.07.010. Epub 2021 Aug 17. PMID: 34407456.
Current directions in tau research: Highlights from Tau 2020
Sexton C, Snyder H, Beher D, Boxer AL, Brannelly P, Brion JP, Buée L, Cacace AM, Chételat G, Citron M, DeVos SL, Diaz K, Feldman HH, Frost B, Goate AM, Gold M, Hyman B, Johnson K, Karch CM, Kerwin DR, Koroshetz WJ, Litvan I, Morris HR, Mummery CJ, Mutamba J, Patterson MC, Quiroz YT, Rabinovici GD, Rommel A, Shulman MB, Toledo-Sherman LM, Weninger S, Wildsmith KR, Worley SL, Carrillo MC. Current directions in tau research: Highlights from Tau 2020. Alzheimers Dement. 2021 Sep 28. doi: 10.1002/alz.12452. Epub ahead of print. PMID: 34581500.
ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids
Bowles KR, Silva MC, Whitney K, Bertucci T, Berlind JE, Lai JD, Garza JC, Boles NC, Mahali S, Strang KH, Marsh JA, Chen C, Pugh DA, Liu Y, Gordon RE, Goderie SK, Chowdhury R, Lotz S, Lane K, Crary JF, Haggarty SJ, Karch CM, Ichida JK, Goate AM, Temple S. ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids. Cell. 2021 Aug 19;184(17):4547-4563.e17. doi: 10.1016/j.cell.2021.07.003. Epub 2021 Jul 26. PMID: 34314701.
Generation of a gene-corrected human isogenic iPSC line from an Alzheimer’s disease iPSC line carrying the London mutation in APP (V717I)
Hernández D, Morgan Schlicht S, Daniszewski M, Karch CM; Dominantly Inherited Alzheimer Network (DIAN), Goate AM, Pébay A. Generation of a gene-corrected human isogenic iPSC line from an Alzheimer’s disease iPSC line carrying the London mutation in APP (V717I). Stem Cell Res. 2021 May;53:102373. doi: 10.1016/j.scr.2021.102373. Epub 2021 Apr 30. PMID: 34088002.
Segregation of functional networks is associated with cognitive resilience in Alzheimer’s disease
Ewers M, Luan Y, Frontzkowski L, Neitzel J, Rubinski A, Dichgans M, Hassenstab J, Gordon BA, Chhatwal JP, Levin J, Schofield P, Benzinger TLS, Morris JC, Goate A, Karch CM, Fagan AM, McDade E, Allegri R, Berman S, Chui H, Cruchaga C, Farlow M, Graff-Radford N, Jucker M, Lee JH, Martins RN, Mori H, Perrin R, Xiong C, Rossor M, Fox NC, O’Connor A, Salloway S, Danek A, Buerger K, Bateman RJ, Habeck C, Stern Y, Franzmeier N; Alzheimer’s Disease Neuroimaging Initiative and the Dominantly Inherited Alzheimer Network. Segregation of functional networks is associated with cognitive resilience in Alzheimer’s disease. Brain. 2021 Aug 17;144(7):2176-2185. doi: 10.1093/brain/awab112. PMID: 33725114; PMCID: PMC8370409.
Acetylated tau inhibits chaperone-mediated autophagy and promotes tau pathology propagation in mice
Caballero B, Bourdenx M, Luengo E, Diaz A, Sohn PD, Chen X, Wang C, Juste YR, Wegmann S, Patel B, Young ZT, Kuo SY, Rodriguez-Navarro JA, Shao H, Lopez MG, Karch CM, Goate AM, Gestwicki JE, Hyman BT, Gan L, Cuervo AM. Acetylated tau inhibits chaperone-mediated autophagy and promotes tau pathology propagation in mice. Nat Commun. 2021 Apr 14;12(1):2238. doi: 10.1038/s41467-021-22501-9. PMID: 33854069; PMCID: PMC8047017.
Longitudinal Accumulation of Cerebral Microhemorrhages in Dominantly Inherited Alzheimer Disease
Joseph-Mathurin N, Wang G, Kantarci K, Jack CR Jr, McDade E, Hassenstab J, Blazey TM, Gordon BA, Su Y, Chen G, Massoumzadeh P, Hornbeck RC, Allegri RF, Ances BM, Berman SB, Brickman AM, Brooks WS, Cash DM, Chhatwal JP, Chui HC, Correia S, Cruchaga C, Farlow MR, Fox NC, Fulham M, Ghetti B, Graff-Radford NR, Johnson KA, Karch CM, Laske C, Lee AKW, Levin J, Masters CL, Noble JM, O’Connor A, Perrin RJ, Preboske GM, Ringman JM, Rowe CC, Salloway S, Saykin AJ, Schofield PR, Shimada H, Shoji M, Suzuki K, Villemagne VL, Xiong C, Yakushev I, Morris JC, Bateman RJ, Benzinger TLS; Dominantly Inherited Alzheimer Network. Longitudinal Accumulation of Cerebral Microhemorrhages in Dominantly Inherited Alzheimer Disease. Neurology. 2021 Mar 23;96(12):e1632-e1645. doi: 10.1212/WNL.0000000000011542. Epub 2021 Jan 25. PMID: 33495373; PMCID: PMC8032370.
Meningeal lymphatics affect microglia responses and anti-Aβ immunotherapy
Da Mesquita S, Papadopoulos Z, Dykstra T, Brase L, Farias FG, Wall M, Jiang H, Kodira CD, de Lima KA, Herz J, Louveau A, Goldman DH, Salvador AF, Onengut-Gumuscu S, Farber E, Dabhi N, Kennedy T, Milam MG, Baker W, Smirnov I, Rich SS; Dominantly Inherited Alzheimer Network, Benitez BA, Karch CM, Perrin RJ, Farlow M, Chhatwal JP, Holtzman DM, Cruchaga C, Harari O, Kipnis J. Meningeal lymphatics affect microglia responses and anti-Aβ immunotherapy. Nature. 2021 May;593(7858):255-260. doi: 10.1038/s41586-021-03489-0. Epub 2021 Apr 28. PMID: 33911285.