ER-mitochondria contacts and cholesterol metabolism are disrupted by disease-associated tau protein
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Proteomics of brain, CSF, and plasma identifies molecular signatures for distinguishing sporadic and genetic Alzheimer’s disease
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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)
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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.
Generation of iPSC-derived human forebrain organoids assembling bilateral eye primordia
Gabriel E, Albanna W, Pasquini G, Ramani A, Josipovic N, Mariappan A, Riparbelli MG, Callaini G, Karch CM, Goureau O, Papantonis A, Busskamp V, Schneider T, Gopalakrishnan J. Generation of iPSC-derived human forebrain organoids assembling bilateral eye primordia. Nat Protoc. 2023 Jun;18(6):1893-1929. doi: 10.1038/s41596-023-00814-x. Epub 2023 May 17. PMID: 37198320.
KATP channels are necessary for glucose-dependent increases in amyloid-β and Alzheimer’s disease-related pathology
Grizzanti J, Moritz WR, Pait MC, Stanley M, Kaye SD, Carroll CM, Constantino NJ, Deitelzweig LJ, Snipes JA, Kellar D, Caesar EE, Pettit-Mee RJ, Day SM, Sens JP, Nicol NI, Dhillon J, Remedi MS, Kiraly DD, Karch CM, Nichols CG, Holtzman DM, Macauley SL. KATP channels are necessary for glucose-dependent increases in amyloid-β and Alzheimer’s disease-related pathology. JCI Insight. 2023 May 2;8(10):e162454. doi: 10.1172/jci.insight.162454. PMID: 37129980; PMCID: PMC10386887.
Defects in lysosomal function and lipid metabolism in human microglia harboring a TREM2 loss of function mutation
Filipello F, You SF, Mirfakhar FS, Mahali S, Bollman B, Acquarone M, Korvatska O, Marsh JA, Sivaraman A, Martinez R, Cantoni C, De Feo L, Ghezzi L, Minaya MA, Renganathan A, Cashikar AG, Satoh JI, Beatty W, Iyer AK, Cella M, Raskind WH, Piccio L, Karch CM. Defects in lysosomal function and lipid metabolism in human microglia harboring a TREM2 loss of function mutation. Acta Neuropathol. 2023 Jun;145(6):749-772. doi: 10.1007/s00401-023-02568-y. Epub 2023 Apr 28. PMID: 37115208; PMCID: PMC10175346.
Large multi-ethnic genetic analyses of amyloid imaging identify new genes for Alzheimer disease
Ali M, Archer DB, Gorijala P, Western D, Timsina J, Fernández MV, Wang TC, Satizabal CL, Yang Q, Beiser AS, Wang R, Chen G, Gordon B, Benzinger TLS, Xiong C, Morris JC, Bateman RJ, Karch CM, McDade E, Goate A, Seshadri S, Mayeux RP, Sperling RA, Buckley RF, Johnson KA, Won HH, Jung SH, Kim HR, Seo SW, Kim HJ, Mormino E, Laws SM, Fan KH, Kamboh MI, Vemuri P, Ramanan VK, Yang HS, Wenzel A, Rajula HSR, Mishra A, Dufouil C, Debette S, Lopez OL, DeKosky ST, Tao F, Nagle MW; Knight Alzheimer Disease Research Center (Knight ADRC); Dominantly Inherited Alzheimer Network (DIAN); Alzheimer’s Disease Neuroimaging Initiative (ADNI); ADNI-DOD, A4 Study Team; Australian Imaging Biomarkers, Lifestyle (AIBL) Study; Hohman TJ, Sung YJ, Dumitrescu L, Cruchaga C. Large multi-ethnic genetic analyses of amyloid imaging identify new genes for Alzheimer disease. Acta Neuropathol Commun. 2023 Apr 26;11(1):68. doi: 10.1186/s40478-023-01563-4. PMID: 37101235; PMCID: PMC10134547.
Single-nucleus RNA-sequencing of autosomal dominant Alzheimer disease and risk variant carriers
Brase L, You SF, D’Oliveira Albanus R, Del-Aguila JL, Dai Y, Novotny BC, Soriano-Tarraga C, Dykstra T, Fernandez MV, Budde JP, Bergmann K, Morris JC, Bateman RJ, Perrin RJ, McDade E, Xiong C, Goate AM, Farlow M; Dominantly Inherited Alzheimer Network (DIAN); Sutherland GT, Kipnis J, Karch CM, Benitez BA, Harari O. Single-nucleus RNA-sequencing of autosomal dominant Alzheimer disease and risk variant carriers. Nat Commun. 2023 Apr 21;14(1):2314. doi: 10.1038/s41467-023-37437-5. PMID: 37085492; PMCID: PMC10121712.
Long non-coding RNA SNHG8 drives stress granule formation in tauopathies
Bhagat, R., Minaya, M.A., Renganathan, A. et al. Long non-coding RNA SNHG8 drives stress granule formation in tauopathies. Mol Psychiatry (2023). https://doi.org/10.1038/s41380-023-02237-2
Conserved gene signatures shared among MAPT mutations reveal defects in calcium signaling
Minaya MA, Mahali S, Iyer AK, Eteleeb AM, Martinez R, Huang G, Budde J, Temple S, Nana AL, Seeley WW, Spina S, Grinberg LT, Harari O, Karch CM. Conserved gene signatures shared among MAPT mutations reveal defects in calcium signaling. Front Mol Biosci. 2023 Feb 9;10:1051494. doi: 10.3389/fmolb.2023.1051494. PMID: 36845551; PMCID: PMC9948093.
Change in Cerebrospinal Fluid Tau Microtubule Binding Region Detects Symptom Onset, Cognitive Decline, Tangles, and Atrophy in Dominantly Inherited Alzheimer’s Disease
Horie K, Li Y, Barthélemy NR, Gordon B, Hassenstab J, Benzinger TLS, Fagan AM, Morris JC, Karch CM, Xiong C, Allegri R, Mendez PC, Ikeuchi T, Kasuga K, Noble J, Farlow M, Chhatwal J, Day G, Schofield PR, Masters CL, Levin J, Jucker M, Lee JH, Roh JH, Sato C, Sachdev P, Koyama A, Reyderman L, Bateman RJ, McDade E; Dominantly Inherited Alzheimer Network. Change in Cerebrospinal Fluid Tau Microtubule Binding Region Detects Symptom Onset, Cognitive Decline, Tangles, and Atrophy in Dominantly Inherited Alzheimer’s Disease. Ann Neurol. 2023 Jun;93(6):1158-1172. doi: 10.1002/ana.26620. Epub 2023 Mar 16. PMID: 36843330; PMCID: PMC10238659.
Brain network decoupling with increased serum neurofilament and reduced cognitive function in Alzheimer’s disease
Wheelock MD, Strain JF, Mansfield P, Tu JC, Tanenbaum A, Preische O, Chhatwal JP, Cash DM, Cruchaga C, Fagan AM, Fox NC, Graff-Radford NR, Hassenstab J, Jack CR, Karch CM, Levin J, McDade EM, Perrin RJ, Schofield PR, Xiong C, Morris JC, Bateman RJ, Jucker M, Benzinger TLS, Ances BM, Eggebrecht AT, Gordon BA; Dominantly Inherited Alzheimer Network. Brain network decoupling with increased serum neurofilament and reduced cognitive function in Alzheimer’s disease. Brain. 2023 Jul 3;146(7):2928-2943. doi: 10.1093/brain/awac498. PMID: 36625756; PMCID: PMC10316768.
Plasma glial fibrillary acidic protein in autosomal dominant Alzheimer’s disease: Associations with Aβ-PET, neurodegeneration, and cognition
Chatterjee P, Vermunt L, Gordon BA, Pedrini S, Boonkamp L, Armstrong NJ, Xiong C, Singh AK, Li Y, Sohrabi HR, Taddei K, Molloy M, Benzinger TLS, Morris JC, Karch C, Berman S, Chhatwal J, Cruchaga C, Graff-Radford NR, Day GS, Farlow M, Fox N, Goate A, Hassenstab J, Lee JH, Levin J, McDade E, Mori H, Perrin R, Sanchez-Valle R, Schofield PR, Levey A, Jucker M, Masters CL, Fagan AM, Bateman RJ, Martins RN, Teunissen C; Dominantly Inherited Alzheimer Network. Plasma glial fibrillary acidic protein in autosomal dominant Alzheimer’s disease: Associations with Aβ-PET, neurodegeneration, and cognition. Alzheimers Dement. 2023 Jul;19(7):2790-2804. doi: 10.1002/alz.12879. Epub 2022 Dec 28. PMID: 36576155; PMCID: PMC10300233.
Defective proteostasis in induced pluripotent stem cell models of frontotemporal lobar degeneration
Mahali S, Martinez R, King M, Verbeck A, Harari O, Benitez BA, Horie K, Sato C, Temple S, Karch CM. Defective proteostasis in induced pluripotent stem cell models of frontotemporal lobar degeneration. Transl Psychiatry. 2022 Dec 10;12(1):508. doi: 10.1038/s41398-022-02274-5. PMID: 36494352; PMCID: PMC9734180.
CSF tau microtubule-binding region identifies pathological changes in primary tauopathies
Horie K, Barthélemy NR, Spina S, VandeVrede L, He Y, Paterson RW, Wright BA, Day GS, Davis AA, Karch CM, Seeley WW, Perrin RJ, Koppisetti RK, Shaikh F, Lago AL, Heuer HW, Ghoshal N, Gabelle A, Miller BL, Boxer AL, Bateman RJ, Sato C. CSF tau microtubule-binding region identifies pathological changes in primary tauopathies. Nat Med. 2022 Dec;28(12):2547-2554. doi: 10.1038/s41591-022-02075-9. Epub 2022 Nov 24. PMID: 36424467; PMCID: PMC9800273.
Parenchymal border macrophages regulate the flow dynamics of the cerebrospinal fluid
Drieu A, Du S, Storck SE, Rustenhoven J, Papadopoulos Z, Dykstra T, Zhong F, Kim K, Blackburn S, Mamuladze T, Harari O, Karch CM, Bateman RJ, Perrin R, Farlow M, Chhatwal J; Dominantly Inherited Alzheimer Network; Hu S, Randolph GJ, Smirnov I, Kipnis J. Parenchymal border macrophages regulate the flow dynamics of the cerebrospinal fluid. Nature. 2022 Nov;611(7936):585-593. doi: 10.1038/s41586-022-05397-3. Epub 2022 Nov 9. PMID: 36352225; PMCID: PMC9899827.
17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes
Bowles KR, Pugh DA, Liu Y, Patel T, Renton AE, Bandres-Ciga S, Gan-Or Z, Heutink P, Siitonen A, Bertelsen S, Cherry JD, Karch CM, Frucht SJ, Kopell BH, Peter I, Park YJ; International Parkinson’s Disease Genomics Consortium (IPDGC); Charney A, Raj T, Crary JF, Goate AM. 17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes. Mol Neurodegener. 2022 Jul 15;17(1):48. doi: 10.1186/s13024-022-00551-x. PMID: 35841044; PMCID: PMC9284779.
Metabolomic and lipidomic signatures in autosomal dominant and late-onset Alzheimer’s disease brains
Novotny BC, Fernandez MV, Wang C, Budde JP, Bergmann K, Eteleeb AM, Bradley J, Webster C, Ebl C, Norton J, Gentsch J, Dube U, Wang F, Morris JC, Bateman RJ, Perrin RJ, McDade E, Xiong C, Chhatwal J; Dominantly Inherited Alzheimer Network (DIAN) Study Group; Alzheimer’s Disease Neuroimaging Initiative; Alzheimer’s Disease Metabolomics Consortium (ADMC); Goate A, Farlow M, Schofield P, Chui H, Karch CM, Cruchaga C, Benitez BA, Harari O. Metabolomic and lipidomic signatures in autosomal dominant and late-onset Alzheimer’s disease brains. Alzheimers Dement. 2023 May;19(5):1785-1799. doi: 10.1002/alz.12800. Epub 2022 Oct 17. PMID: 36251323; PMCID: PMC10106526.