2025
The neuropathologic basis for translational biomarker development in the macaque model of late-onset Alzheimer's disease
Zeiss C, Huttner A, Nairn A, Arnsten A, Datta D, Strittmatter S, Vander Wyk B, Duque A. The neuropathologic basis for translational biomarker development in the macaque model of late-onset Alzheimer's disease. Journal Of Alzheimer’s Disease 2025, 104: 1243-1258. PMID: 40095666, DOI: 10.1177/13872877251323787.Peer-Reviewed Original ResearchAlzheimer's diseaseLate-onset Alzheimer's diseaseModel of late-onset Alzheimer's diseaseBraak stages III-IVDisruption of synaptic connectivityFormalin Fixed ParaffinAccumulation of senescence markersTau phosphorylationAmyloid-bFibrillar tauSenescence markersCo-morbiditiesPTau expressionLabile proteinBiomarker developmentStage III-IVSynaptic disruptionGlial fibrillary acidic proteinSenescence markers p16Fibrillary acidic proteinPredictive biomarkersFFPE tissuesMacaque modelAcidic proteinIII-IVBrain morphology mediating the effects of common genetic risk variants on Alzheimer's disease.
Breddels E, Snihirova Y, Pishva E, Gülöksüz S, Blokland G, Luykx J, Andreassen O, Linden D, van der Meer D. Brain morphology mediating the effects of common genetic risk variants on Alzheimer's disease. Journal Of Alzheimer's Disease Reports 2025, 9: 25424823251328300. PMID: 40144144, PMCID: PMC11938454, DOI: 10.1177/25424823251328300.Peer-Reviewed Original ResearchLate-onset Alzheimer's diseaseGenetic risk variantsMendelian randomizationRisk of late-onset Alzheimer's diseaseInferior lateral ventricleUK BiobankAlzheimer's Disease Neuroimaging InitiativeCausal pathwaysAlzheimer's diseaseRisk variantsClinical dataLateral ventricleNeurobiological pathwaysBiobankAlzheimerGenetic dataDiseaseAssociated with alterationsGenetic variationBrain morphologyEntorhinal cortexRiskMeasures of brain morphology
2024
The early-onset Alzheimer’s disease MRI signature: a replication and extension analysis in early-stage AD
Mehta R, Keith C, Teixeira C, Worhunsky P, Phelps H, Ward M, Miller M, Navia R, Pockl S, Rajabalee N, Coleman M, D’Haese P, Rezai A, Wilhelmsen K, Haut M. The early-onset Alzheimer’s disease MRI signature: a replication and extension analysis in early-stage AD. Cerebral Cortex 2024, 34: bhae475. PMID: 39714256, PMCID: PMC11664631, DOI: 10.1093/cercor/bhae475.Peer-Reviewed Original ResearchConceptsEarly-onset Alzheimer's diseaseLate-onset Alzheimer's diseaseNon-AD pathologyCognitively normal individualsManagement of personsCortical atrophyFunctional statusEarly-stage ADRural populationAlzheimer's diseaseDisease stageLongitudinal studyCortical signatureWhole-brainCortical thinningCortical analysisClinical cohortNormal individualsClinical effectsSignature regionsIndividualsPersonsEarly disease stagesMRI signaturesA Multi‐Omic Analysis of Molecular Risk and Resilience Factors in Late‐Onset Alzheimer’s Disease in APOEe4 Carriers
Markov Y, Priyanka A, Higgins‐Chen A. A Multi‐Omic Analysis of Molecular Risk and Resilience Factors in Late‐Onset Alzheimer’s Disease in APOEe4 Carriers. Alzheimer's & Dementia 2024, 20: e092941. PMCID: PMC11709863, DOI: 10.1002/alz.092941.Peer-Reviewed Original ResearchLate-onset Alzheimer's diseaseMulti-omics analysisApolipoprotein ESusceptible to AD pathologyDisease resilienceDeep whole-exome sequencingMulti-omics datasetsDNA methylation profilesAlzheimer's diseaseWhole-exome sequencingMolecular signaturesLabel-free mass spectrometryIllumina EPIC arrayDNA methylationExome sequencingMethylation profilesEPIC arrayOmics levelsReligious Orders StudyAD pathologyMulti-tissueMutated genesGenesE4 alleleExtracellular matrixTowards cascading genetic risk in Alzheimer’s disease
Altmann A, Aksman L, Oxtoby N, Young A, Weiner M, Aisen P, Petersen R, Weiner M, Aisen P, Petersen R, Jack C, Jagust W, Landau S, Rivera-Mindt M, Okonkwo O, Shaw L, Lee E, Toga A, Beckett L, Harvey D, Green R, Saykin A, Nho K, Perrin R, Tosun D, Sachdev P, Green R, Montine T, Conti C, Weiner M, Nosheny R, Fockler J, Miller M, Conti C, Kwang W, Jin C, Diaz A, Ashford M, Flenniken D, Kormos A, Petersen R, Aisen P, Rafii M, Raman R, Jimenez G, Donohue M, Salazar J, Fidell A, Boatwright V, Robison J, Zimmerman C, Cabrera Y, Walter S, Clanton T, Shaffer E, Webb C, Hergesheimer L, Smith S, Ogwang S, Adegoke O, Mahboubi P, Pizzola J, Jenkins C, Beckett L, Harvey D, Donohue M, Saito N, Diaz A, Hussen K, Okonkwo O, Rivera-Mindt M, Amaza H, Thao M, Parkins S, Ayo O, Glittenberg M, Hoang I, Germano K, Strong J, Weisensel T, Magana F, Thomas L, Guzman V, Ajayi A, Benedetto J, Talavera S, Jack C, Felmlee J, Fox N, Thompson P, DeCarli C, Forghanian-Arani A, Borowski B, Reyes C, Hedberg C, Ward C, Schwarz C, Reyes D, Gunter J, Moore-Weiss J, Kantarci K, Matoush L, Senjem M, Vemuri P, Reid R, Malone I, Thomopoulos S, Nir T, Jahanshad N, Knaack A, Fletcher E, Harvey D, Tosun-Turgut D, Chen S, Choe M, Crawford K, Yushkevich P, Das S, Jagust W, Landau S, Koeppe R, Rabinovici G, Villemagne V, LoPresti B, Perrin R, Morris J, Franklin E, Bernhardt H, Cairns N, Taylor-Reinwald L, Shaw L, Lee E, Virginia Lee M, Korecka M, Brylska M, Wan Y, Trojanowki J, Toga A, Crawford K, Neu S, Saykin A, Nho K, Foroud T, Jo T, Risacher S, Craft H, Apostolova L, Nudelman K, Faber K, Potter Z, Lacy K, Kaddurah-Daouk R, Shen L, Karlawish J, Erickson C, Grill J, Largent E, Harkins K, Weiner M, Thal L, Kachaturian Z, Frank R, Snyder P, Buckholtz N, Hsiao J, Ryan L, Molchan S, Khachaturian Z, Carrillo M, Potter W, Barnes L, Bernard M, González H, Ho C, Hsiao J, Jackson J, Masliah E, Masterman D, Okonkwo O, Perrin R, Ryan L, Silverberg N, Silbert L, Kaye J, White S, Pierce A, Thomas A, Clay T, Schwartz D, Devereux G, Taylor J, Ryan J, Nguyen M, DeCapo M, Shang Y, Schneider L, Munoz C, Ferman D, Conant C, Martin K, Oleary K, Pawluczyk S, Trejo E, Dagerman K, Teodoro L, Becerra M, Fairooz M, Garrison S, Boudreau J, Avila Y, Brewer J, Jacobson A, Gama A, Kim C, Little E, Frascino J, Ferng N, Trujillo S, Heidebrink J, Koeppe R, MacDonald S, Malyarenko D, Ziolkowski J, O'Connor J, Robert N, Lowe S, Rogers V, Petersen R, Hackenmiller B, Boeve B, Albers C, Kreuger C, Jones D, Knopman D, Botha H, Magnuson J, Graff-Radford J, Crawley K, Schumacher M, McKinzie S, Smith S, Helland T, Lowe V, Ramanan V, Pavlik V, Faircloth J, Bishop J, Nath J, Chaudhary M, Kataki M, Yu M, Pacini N, Barker R, Brooks R, Aggarwal R, Honig L, Stern Y, Mintz A, Cordona J, Hernandez M, Long J, Arnold A, Groves A, Middleton A, Vogler B, McCurry C, Mayo C, Raji C, Amtashar F, Klemp H, Elmore H, Ruszkiewicz J, Kusuran J, Stewart J, Horenkamp J, Greeson J, Wever K, Vo K, Larkin K, Rao L, Schoolcraft L, Gallagher L, Paczynski 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Boonsiri J, Kenowsky S, Martinez T, Briglall V, Doraiswamy P, Nwosu A, Adhikari A, Hellegers C, Petrella J, James O, Wong T, Hawk T, Vaishnavi S, McCoubrey H, Nasrallah I, Rovere R, Maneval J, Robinson E, Rivera F, Uffelman J, Combs M, O'Donnell P, Manning S, King R, Nieto A, Glueck A, Mandal A, Swain A, Gamble B, Meacham B, Forenback D, Ross D, Cheatham E, Hartman E, Cornell G, Harp J, Ashe L, Goins L, Watts L, Yazell M, Mandal P, Buckler R, Vincent S, Rudd T, Lopez O, Malia A, Chiado C, Zik C, Ruszkiewicz J, Savage K, Fenice L, Oakley M, Tacey P, Berman S, Bowser S, Hegedus S, Saganis X, Porsteinsson A, Mathewson A, Widman A, Holvey B, Clark E, Morales E, Young I, Ruszkiewicz J, Hopkins K, Martin K, Kowalski N, Hunt R, Calzavara R, Kurvach R, D'Ambrosio S, Thai G, Vides B, Lieb B, McAdams-Ortiz C, Toso C, Mares I, Moorlach K, Liu L, Corona M, Nguyen M, Tallakson M, McDonnell M, Rangel M, Basheer N, Place P, Romero R, Tam S, Nguyen T, Thomas A, Frolov A, Khera A, Browning A, Kelley B, Dawson C, Mathews D, Most E, Phillips E, Nguyen L, Nunez M, Miller M, Jones M, Martinez N, Logan R, McColl R, Pham S, Fox T, Moore T, Levey A, Brown A, Kippels A, Ellison A, Lyons C, Hales C, Parry C, Williams C, McCorkle E, Harris G, Rose H, Jooma I, Al-Amin J, Lah J, Webster J, Swiniarski J, Chapman L, Donnelly L, Mariotti L, Locke M, Vaughn P, Penn R, Carpentier S, Yeboah S, Basadre S, Malakauskas S, Lyron S, Villinger T, Burney T, Burns J, Abusalim A, Dahlgren A, Montero A, Arthur A, Dooly H, Kreszyn K, Berner K, Gillen L, Scanlan M, Madison M, Mathis N, Switzer P, Townley R, Fikru S, Sullivan S, Wright E, Beigi M, Daley A, Ko A, Luong B, Nyborg G, Morales J, Durbin K, Garcia L, Parand L, Macias L, Monserratt L, Farchi M, Wu P, Hernandez R, Rodriguez T, Graff-Radford N, Marolt A, Thomas A, Aloszka D, Moncayo E, Westerhold E, Day G, Chrestensen K, Imhansiemhonehi M, McKinzie S, Stephens S, Grant S, Brosch J, Perkins A, Saunders A, Kovac D, Polson H, Mwaura I, Mejia K, Britt K, King K, Nichols K, Lawrence K, Rankin L, Farlow M, Wiesenauer P, Bryant R, Herring S, Lynch S, Wilson S, Day T, Korst W, van Dyck C, Mecca A, Miller A, Brennan A, Khan A, Ruan A, Gunnoud C, Mendonca C, Raynes-Goldfinger D, Salardini E, Hidalgo E, Cooper E, Singh E, Murphy E, May J, Stanhope J, Lam J, Waszak J, Nelsen K, Sacaza K, Hasbani M, Donahue M, Chen M, Barcelos N, Eigenberger P, Bonomi R, O'Dell R, Jefferson S, Khasnavis S, Smilowitz S, DeStefano S, Good S, Camarro T, Clayton V, Cavrel Y, Lu Y, Chertkow H, Bergman H, Hosein C, Black S, Kapadia A, Bhan A, Lam B, Scott C, Gabriel G, Bray J, Zotovic L, Gutierrez M, Masellis M, Farshadi M, Gui M, Mitchell M, Taylor R, Endre R, Taghi-Zada Z, Hsiung R, English C, Kim E, Yau E, Tong H, Barlow L, Jennings L, Assaly M, Nunes P, Marian T, Kertesz A, Rogers J, Trost D, Wint D, Bernick C, Munic D, Grant I, Korkoyah A, Raja A, Lapins A, Ryan C, Pejic J, Basham K, Lukose L, Haddad L, Quinlan L, Houghtaling N, MD C, MD W, MD T, Reynolds B, Forero A, Ward C, Brennan E, Figueroa E, Esposito G, Mallory J, Johnson K, Turner K, Seidenberg K, McCann K, Bassett M, Chadwick M, Turner R, Bean R, Sharma S, Marshall G, Haviari A, Pietras A, Wallace B, Munro C, Rivera-Delpin G, Hustead H, Levesque I, Ramirez J, Nolan K, Glennon K, Palou M, Erkkinen M, DaSilva N, Friedman P, Silver R, Salazar R, Polleys R, McGinnis S, Gale S, Hall T, Luu T, Chao S, Lin E, Coleman J, Epperson K, Vasanawala M, Atri A, Rangel A, Evans B, Monarrez C, Cline C, Liebsack C, Bandy D, Goldfarb D, Intorcia D, Olgin J, Clark K, King K, York K, Reade M, Callan M, Glass M, Johnson M, Gutierrez M, Goddard M, Trncic N, Choudhury P, Reyes P, Lowery S, Hall S, Olgin S, de Santiago S, Alosco M, Ton A, Jimenez A, Ellison A, Tran A, Anderson B, Carter D, Veronelli D, Lenio S, Steinberg E, Mez J, Weller J, Johns J, Mez J, Harkins J, Puleio A, Hoti I, Mwicigi J, Puleio A, Alosco M, Schultz O, Lauture M, Steinberg E, Denis R, Killiany R, Singh S, Lenio S, Qiu W, Devis Y, Obisesan T, Stone A, Ordor D, Udodong I, Okonkwo I, Khan J, Turner J, Hughes K, Kadiri O, Duffy C, Moss A, Stapleton K, Toth M, Sanders M, Ayres M, Hamski M, Fatica P, Ogrocki P, Ash S, Pot S, Chen D, Soto A, Tanase C, Bissig D, Vanya H, Russell H, Patel H, Zhang H, Wallace K, Ayers K, Gallegos M, Forloines M, Sinn M, Kahulugan Q, Isip R, Calderon S, Hamm T, Borrie M, Lee T, Bartha R, Johnson S, Asthana S, Carlsson C, Perrin A, Tariot P, Fleisher A, Reeder S, Capote H, Emborsky A, Mattle A, Ajtai B, Wagner B, Myers B, Slazyk D, Fragale D, Fransen E, Macnamara H, Falletta J, Hirtreiter J, Mechtler L, King M, Asbach M, Rainka M, Zawislak R, Wisniewski S, O'Malley S, Jimenez-Knight T, Peehler T, Aladeen T, Bates V, Wenner V, Elmalik W, Scharre D, Ramamurthy A, Bouchachi S, Kataki M, Tarawneh R, Kelley B, Celmins D, Leader A, Figueroa C, Bauerle H, Patterson K, Reposa M, Presto S, Ahmed T, Stewart W, Pearlson G, Blank K, Anderson K, Santulli R, Schwartz E, Williamson J, Jessup A, Williams A, Duncan C, O'Connell A, Gagnon K, Zamora E, Bateman J, Crawford F, Thompson D, Walker E, Rowell J, White M, Ledford P, Bohlman S, Henkle S, Bottoms J, Moretz L, Hoover B, Shannon M, Rogers S, Baker W, Harrison W, Wu C, DeMarco A, Stipanovich A, Arcuri D, Clark J, Davis J, Doyon K, Amoyaw M, Acosta M, Bailey R, Warren S, Fogerty T, Sanborn V, Hospital B, Riddle M, Salloway S, Malloy P, Correia S, Windon C, Blackburn M, Rosen H, Miller B, Smith A, Mba I, Echevarria J, Janavs J, Roglaski E, Yong M, Devine R, Okhravi H, Rivera E, Kalowsky T, Smith C, Rosario C, Masdeu J, Le R, Gurung M, Sabbagh M, Garcia A, Slaughter M, Elayan N, Acothley S, Pomara N, Hernando R, Pomara V, Reichert C, Brawman-Mintzer O, Acree A, Williams A, Long C, Long R, Newhouse P, Hill S, Boegel A, Seshadri S, Saklad A, Jones F, Hu W, Sotelo V, Rojas Y, Mintzer J, Longmire C, Spicer K, Alexander D, Barkhof F, Shoai M, Hardy J, Schott J. Towards cascading genetic risk in Alzheimer’s disease. Brain 2024, 147: 2680-2690. PMID: 38820112, PMCID: PMC11292901, DOI: 10.1093/brain/awae176.Peer-Reviewed Original ResearchConceptsLate-onset Alzheimer's diseaseAlzheimer's diseaseGenetic riskDevelopment of late-onset Alzheimer's diseaseGenome-wide association studiesPolygenic riskAlzheimer's Disease Neuroimaging Initiative cohortPolygenic risk scoresStage-dependent fashionAssociation studiesYears of educationCox proportional hazards modelsAPOE effectsProportional hazards modelA+TContribution of apoEAPOE-e4Targeted interventionsMolecular processesATN frameworkE4 homozygotesRisk scoreStage-dependent effectsInitiative cohortAlzheimerSupervised latent factor modeling isolates cell-type-specific transcriptomic modules that underlie Alzheimer’s disease progression
Hodgson L, Li Y, Iturria-Medina Y, Stratton J, Wolf G, Krishnaswamy S, Bennett D, Bzdok D. Supervised latent factor modeling isolates cell-type-specific transcriptomic modules that underlie Alzheimer’s disease progression. Communications Biology 2024, 7: 591. PMID: 38760483, PMCID: PMC11101463, DOI: 10.1038/s42003-024-06273-8.Peer-Reviewed Original ResearchConceptsGene programAlzheimer's diseaseLate-onset Alzheimer's diseaseAD risk lociCell type-specificSingle-nucleus RNA sequencingRisk lociAD brainAlzheimer's disease progressionSnRNA-seqRNA sequencingAD pathophysiologySignaling cascadesTranscriptome modulationProgressive neurodegenerative diseaseCell-typeGWASNeurodegenerative diseasesNeuronal lossGlial cellsTranscriptomeLociGenesPseudo-trajectoriesDisease progressionWhole genome‐wide sequence analysis of long‐lived families (Long‐Life Family Study) identifies MTUS2 gene associated with late‐onset Alzheimer's disease
Xicota L, Cosentino S, Vardarajan B, Mayeux R, Perls T, Andersen S, Zmuda J, Thyagarajan B, Yashin A, Wojczynski M, Krinsky‐McHale S, Handen B, Christian B, Head E, Mapstone M, Schupf N, Lee J, Barral S, Study T, Abner E, Adams P, Aguirre A, Albert M, Albin R, Allen M, Alvarez L, Andrews H, Apostolova L, Arnold S, Asthana S, Atwood C, Ayres G, Barber R, Barnes L, Barral S, Bartlett J, Beach T, Becker J, Beecham G, Benchek P, Bennett D, Bertelson J, Biber S, Bird T, Blacker D, Boeve B, Bowen J, Boxer A, Brewer J, Burke J, Burns J, Bush W, Buxbaum J, Byrd G, Cantwell L, Cao C, Carlsson C, Carrasquillo M, Chan K, Chasse S, Chen Y, Chesselet M, Chin N, Chui H, Chung J, Craft S, Crane P, Cranney M, Cruchaga C, Cuccaro M, Culhane J, Cullum C, Darby E, Davis B, De Jager P, DeCarli C, DeToledo J, Dickson D, Dobbins N, Duara R, Ertekin‐Taner N, Evans D, Faber K, Fairchild T, Fallin D, Fallon K, Fardo D, Farlow M, Farrell J, Farrer L, Fernandez‐Hernandez V, Foroud T, Frosch M, Galasko D, Gamboa A, Gauthreaux K, Gefen T, Geschwind D, Ghetti B, Gilbert J, Goate A, Grabowski T, Graff‐Radford N, Griswold A, Haines J, Hakonarson H, Hall K, Hall J, Hamilton R, Hamilton‐Nelson K, Han X, Harari O, Hardy J, Harrell L, Head E, Henderson V, Hernandez M, Honig L, Huebinger R, Huentelman M, Hulette C, Hyman B, Hynan L, Ibanez L, Jarvik G, Jayadev S, Jin L, Johnson K, Johnson L, Jones B, Jun G, Kamboh M, Kang M, Karydas A, Katz M, Kauwe J, Kaye J, Keene C, Keller B, Khaleeq A, Kim R, Knebl J, Kowall N, Kramer J, Kukull W, Kunkle B, Kuzma A, LaFerla F, Lah J, Larson E, Lerch M, Lerner A, Leung Y, Leverenz J, Levey A, Lieberman A, Lipton R, Lopez O, Lunetta K, Lyketsos C, Mains D, Manly J, Mark L, Marquez D, Marson D, Martin E, Masliah E, Massman P, Masurkar A, Mayeux R, McCormick W, McCurry S, McDonough S, McKee A, Mesulam M, Mez J, Miller B, Miller C, Mock C, Moghekar A, Montine T, Monuki E, Mooney S, Morris J, Mukherjee S, Myers A, Naj A, Nguyen T, Noble J, Nudelman K, O'Bryant S, Ormsby K, Ory M, Palmer R, Parisi J, Paulson H, Pavlik V, Paydarfar D, Perez V, Pericak‐Vance M, Petersen R, Polk M, Qu L, Quiceno M, Quinn J, Raj A, Rajabli F, Ramanan V, Reiman E, Reisch J, Reitz C, Ringman J, Roberson E, Rodriguear M, Rogaeva E, Rosen H, Rosenberg R, Royall D, Sano M, Saykin A, Schellenberg G, Schneider J, Schneider L, Seeley W, Sherva R, Shibata D, Small S, Smith A, Smith J, Song Y, Spina S, St George‐Hyslop P, Stern R, Stevens A, Strittmatter S, Sultzer D, Swerdlow R, Teich A, Tilson J, Tosto G, Trojanowski J, Troncoso J, Tsuang D, Valladares O, Van Deerlin V, Van Dyck C, Van Eldik L, Vance J, Vardarajan B, Vassar R, Vinters H, Wang L, Weintraub S, Welsh‐Bohmer K, Wheeler N, Wijsman E, Wilhelmsen K, Williams B, Williamson J, Wilms H, Wingo T, Wisniewski T, Woltjer R, Woon M, Younkin S, Yu L, Zhao Y, Zhou X, Zhu C, Aizenstein H, Ances B, Andrews H, Bell K, Birn R, Brickman A, Bulova P, Cheema A, Chen K, Christian B, Clare I, Cohen A, Constantino J, Doran E, Fagan A, Feingold E, Foroud T, Handen B, Harp J, Hartley S, Head E, Henson R, Hom C, Honig L, Ikonomovic M, Johnson S, Jordan C, Kamboh M, Keator D, Klunk W, Kofler J, Krinsky‐McHale S, Lai F, Lao P, Laymon C, Lee J, Lott I, Lupson V, Mapstone M, Mathis C, Minhas D, Nadkarni N, O'Bryant S, Parisi M, Pang D, Petersen M, Price J, Pulsifer M, Rafii M, Reiman E, Rizvi B, Rosas H, Ryan L, Schmitt F, Schupf N, Silverman W, Tudorascu D, Tumuluru R, Varadarajan B, White D, Yassa M, Zaman S, Zhang F. Whole genome‐wide sequence analysis of long‐lived families (Long‐Life Family Study) identifies MTUS2 gene associated with late‐onset Alzheimer's disease. Alzheimer's & Dementia 2024, 20: 2670-2679. PMID: 38380866, PMCID: PMC11032545, DOI: 10.1002/alz.13718.Peer-Reviewed Original ResearchConceptsLate-onset Alzheimer's diseaseGenes associated with late-onset Alzheimer's diseaseLate-onset Alzheimer's disease riskSeveral single nucleotide polymorphismsVariants associated with late-onset Alzheimer diseaseBeta-amyloidIdentified several single nucleotide polymorphismsWhole-genome sequence analysisGenome sequence analysisLevels of beta-amyloidAlzheimer's diseaseTight linkage disequilibriumMicrotubule associated proteinSingle nucleotide polymorphismsFamily studiesCandidate lociMTUS2Linkage disequilibriumSequence analysisAssociation analysisNucleotide polymorphismsGenetic associationAlzheimer's dementiaAssociated proteinGenetic component
2023
Etiology of White Matter Hyperintensities in Autosomal Dominant and Sporadic Alzheimer Disease
Shirzadi Z, Schultz S, Yau W, Joseph-Mathurin N, Fitzpatrick C, Levin R, Kantarci K, Preboske G, Jack C, Farlow M, Hassenstab J, Jucker M, Morris J, Xiong C, Karch C, Levey A, Gordon B, Schofield P, Salloway S, Perrin R, McDade E, Levin J, Cruchaga C, Allegri R, Fox N, Goate A, Day G, Koeppe R, Chui H, Berman S, Mori H, Sanchez-Valle R, Lee J, Rosa-Neto P, Ruthirakuhan M, Wu C, Swardfager W, Benzinger T, Sohrabi H, Martins R, Bateman R, Johnson K, Sperling R, Greenberg S, Schultz A, Chhatwal J, Weiner M, Aisen P, Petersen R, Jack C, Jagust W, Trojanowki J, Toga A, Beckett L, Green R, Saykin A, Morris J, Perrin R, Shaw L, Khachaturian Z, Carrillo M, Potter W, Barnes L, Bernard M, González H, Ho C, Hsiao J, Jackson J, Masliah E, Masterman D, Okonkwo O, Ryan L, Silverberg N, Fleisher A, Sacrey D, Fockler J, Conti C, Veitch D, Neuhaus J, Jin C, Nosheny R, Ashford M, Flenniken D, Kormos A, Montine T, Rafii M, Raman R, Jimenez G, Donohue M, Gessert D, Salazar J, Zimmerman C, Cabrera Y, Walter S, Miller G, Coker G, Clanton T, Hergesheimer L, Smith S, Adegoke O, Mahboubi P, Moore S, Pizzola J, Shaffer E, Sloan B, Harvey D, Forghanian-Arani A, Borowski B, Ward C, Schwarz C, Jones D, Gunter J, Kantarci K, Senjem M, Vemuri P, Reid R, Fox N, Malone I, Thompson P, Thomopoulos S, Nir T, Jahanshad N, DeCarli C, Knaack A, Fletcher E, Tosun-Turgut D, Chen S, Choe M, Crawford K, Yushkevich P, Das S, Koeppe R, Reiman E, Chen K, Mathis C, Landau S, Cairns N, Householder E, Franklin E, Bernhardt H, Taylor-Reinwald L, Korecka M, Figurski M, Neu S, Nho K, Risacher S, Apostolova L, Shen L, Foroud T, Nudelman K, Faber K, Wilmes K, Thal L, Silbert L, Lind B, Crissey R, Kaye J, Carter R, Dolen S, Quinn J, Schneider L, Pawluczyk S, Becerra M, Teodoro L, Dagerman K, Spann B, Brewer J, Vanderswag H, Ziolkowski J, Heidebrink J, Zbizek-Nulph L, Lord J, Mason S, Albers C, Knopman D, Johnson K, Villaneuva-Meyer J, Pavlik V, Pacini N, Lamb A, Kass J, Doody R, Shibley V, Chowdhury M, Rountree S, Dang M, Stern Y, Honig L, Mintz A, Ances B, Winkfield D, Carroll M, Stobbs-Cucchi G, Oliver A, Creech M, Mintun M, Schneider S, Geldmacher D, Love M, Griffith R, Clark D, Brockington J, Marson D, Grossman H, Goldstein M, Greenberg J, Mitsis E, Shah R, Lamar M, Samuels P, Duara R, Greig-Custo M, Rodriguez R, Albert M, Onyike C, Farrington L, Rudow S, Brichko R, Kielb S, Smith A, Raj B, Fargher K, Sadowski M, Wisniewski T, Shulman M, Faustin A, Rao J, Castro K, Ulysse A, Chen S, Sheikh M, Singleton-Garvin J, Doraiswamy P, Petrella J, James O, Wong T, Borges-Neto S, Karlawish J, Wolk D, Vaishnavi S, Clark C, Arnold S, Smith C, Jicha G, El Khouli R, Raslau F, Lopez O, Oakley M, Simpson D, Porsteinsson A, Martin K, Kowalski N, Keltz M, Goldstein B, Makino K, Ismail M, Brand C, Thai G, Pierce A, Yanez B, Sosa E, Witbracht M, Kelley B, Nguyen T, Womack K, Mathews D, Quiceno M, Levey A, Lah J, Hajjar I, Cellar J, Burns J, Swerdlow R, Brooks W, Silverman D, Kremen S, Tingus K, Lu P, Bartzokis 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R, Johnson S, Asthana S, Carlsson C, Perrin A, Burke A, Scharre D, Kataki M, Tarawneh R, Hart D, Zimmerman E, Celmins D, Miller D, Boles Ponto L, Smith K, Koleva H, Shim H, Nam K, Schtulz S, Williamson J, Craft S, Cleveland J, Yang M, Sink K, Ott B, Drake J, Tremont G, Daiello L, Ritter A, Bernick C, Munic D, O'Connell A, Mintzer J, Wiliams A, Masdeu J, Shi J, Garcia A, Newhouse P, Potkin S, Salloway S, Malloy P, Correia S, Kittur S, Pearlson G, Blank K, Anderson K, Flashman L, Seltzer M, Hynes M, Santulli R, Relkin N, Chiang G, Lee A, Lin M, Ravdin L, Sood A, Blanchard K, Fleischman D, Arfanakis K, Varon D, Greig M, Goldstein B, Martin K, Reist C, Sadowsky C, Martinez W, Villena T, Rosen H, Marshall G, Peskind E, Petrie E, Li G, Noble J, Voglein J, Chrem Mendez P, Surace E, Ikonomovic S, Nadkarni N, Lopera F, Ramirez L, Aguillon D, Leon Y, Ramos C, Alzate D, Baena A, Londono N, Moreno S, Laske C, Kuder-Buletta E, Graber-Sultan S, Preische O, Hofmann A, Ikeuchi T, Kasuga K, Niimi Y, Ishii K, Senda M, Cash D, Roh J, Riddle M, Menard W, Bodge C, Surti M, Takada L, Farlow M, Sanchez-Gonzalez V, Orozco-Barajas M, Renton A, Esposito B, Karch C, Marsh J, Fernanadez V, Jerome G, Herries E, Llibre-Guerra J, Johnson E, Seyfried N, Brooks W, Bechara J, Franklin E, Chen A, Chen C, Flores S, Hantler N, Hornbeck R, Jarman S, Keefe S, Koudelis D, Massoumzadeh P, McCullough A, McKay N, Nicklaus J, Pulizos C, Wang Q, Mishall S, Sabaredzovic E, Deng E, Candela M, Smith H, Hobbs D, Scott J, Xiong C, Wang P, Xu X, Li Y, Gremminger E, Ma Y, Bui R, Lu R, Martins R, Sosa Ortiz A, Daniels A, Courtney L, Mori H, Supnet-Bell, PhD (CSB) C, Xu J, Ringman J, Barthelemy N, Smith J. Etiology of White Matter Hyperintensities in Autosomal Dominant and Sporadic Alzheimer Disease. JAMA Neurology 2023, 80: 1353-1363. PMID: 37843849, PMCID: PMC10580156, DOI: 10.1001/jamaneurol.2023.3618.Peer-Reviewed Original ResearchConceptsSystemic vascular riskAutosomal dominant Alzheimer's diseaseLate-onset Alzheimer's diseaseVascular riskWMH volumeGray matter volumeAlzheimer's diseaseCohort studyOlder adultsDisease Neuroimaging InitiativeMAIN OUTCOMEMatter volumeCommon magnetic resonance imaging findingCommunity-based medical centerSystemic vascular risk factorsMagnetic resonance imaging (MRI) findingsWhite matter hyperintensity volumeHarvard Aging Brain StudyVascular risk factorsResonance Imaging FindingsLongitudinal cohort studyGreater WMH volumeSporadic Alzheimer's diseasePathogenic variant carriersWhite matter hyperintensities
2022
Alzheimer’s Disease Polygenic Risk Score Is Not Associated With Cognitive Decline Among Older Adults With Type 2 Diabetes
Manzali S, Yu E, Ravona-Springer R, Livny A, Golan S, Ouyang Y, Lesman-Segev O, Liu L, Ganmore I, Alkelai A, Gan-Or Z, Lin H, Heymann A, Beeri M, Greenbaum L. Alzheimer’s Disease Polygenic Risk Score Is Not Associated With Cognitive Decline Among Older Adults With Type 2 Diabetes. Frontiers In Aging Neuroscience 2022, 14: 853695. PMID: 36110429, PMCID: PMC9468264, DOI: 10.3389/fnagi.2022.853695.Peer-Reviewed Original ResearchAssociations of polygenic risk scoresPolygenic risk scoresLate-onset Alzheimer's diseaseOlder adultsAlzheimer’s disease polygenic risk scoreCognitive declineType 2 diabetesGlobal cognitionAssociated with overall functioningRisk scoreRate of cognitive declineDomains of episodic memoryAssociated with cognitive declineVolumes of total gray matterMultiple risk lociSpecific cognitive domainsLanguage/semantic categorizationOverall cognitive functionAlzheimer's diseaseTotal gray matterIsrael DiabetesBrain imaging phenotypesOutcome measuresSusceptibility lociAttention/working memory
2021
No evidence for association of Alzheimer’s disease risk loci with the rate of cognitive decline among elderly with type 2 diabetes
Greenbaum L, Manzali S, Ravona‐Springer R, Lin H, Beeri M. No evidence for association of Alzheimer’s disease risk loci with the rate of cognitive decline among elderly with type 2 diabetes. Alzheimer's & Dementia 2021, 17 DOI: 10.1002/alz.050081.Peer-Reviewed Original ResearchPolygenic risk scoresLate-onset Alzheimer's diseaseRate of cognitive declineDisease risk lociCognitive declineType 2 diabetesPopulation of older adultsAssociated with specific cognitive domainsRisk of dementiaRisk lociHippocampal volumeRisk factorsGlobal cognitive functionGlobal cognitive declineMultiple risk lociSpecific cognitive domainsAPOE e4 alleleCardiovascular risk factorsMixed regression modelsAlzheimer’s disease risk lociIsrael DiabetesOlder adultsDiabetes-relatedRisk scoreMagnetic resonance imaging
2020
The calcium‐containing smooth endoplasmic reticulum is a focus of risk factors for early‐ and late‐onset Alzheimer’s disease
Datta D, Mentone S, Morozov Y, van Dyck C, Arnsten A. The calcium‐containing smooth endoplasmic reticulum is a focus of risk factors for early‐ and late‐onset Alzheimer’s disease. Alzheimer's & Dementia 2020, 16 DOI: 10.1002/alz.047651.Peer-Reviewed Original ResearchLate-onset Alzheimer's diseaseAlzheimer's diseaseSmooth endoplasmic reticulumAD pathologyCalcium dysregulationRisk factorsCalcium leakMonkey dorsolateral prefrontal cortexAutosomal dominant Alzheimer's diseaseNeurofibrillary tangle formationGenetic risk factorsMedial temporal lobeDorsolateral prefrontal cortexMonkey DLPFCAD neurodegenerationTangle formationAge-related pathologiesTemporal lobeAnimal modelsAssociation cortexPS2 mutationTherapeutic interventionsBrain regionsEtiological eventInternal calciumTransformative Network Modeling of Multi-omics Data Reveals Detailed Circuits, Key Regulators, and Potential Therapeutics for Alzheimer’s Disease
Wang M, Li A, Sekiya M, Beckmann ND, Quan X, Schrode N, Fernando MB, Yu A, Zhu L, Cao J, Lyu L, Horgusluoglu E, Wang Q, Guo L, Wang YS, Neff R, Song WM, Wang E, Shen Q, Zhou X, Ming C, Ho SM, Vatansever S, Kaniskan HÜ, Jin J, Zhou MM, Ando K, Ho L, Slesinger PA, Yue Z, Zhu J, Katsel P, Gandy S, Ehrlich ME, Fossati V, Noggle S, Cai D, Haroutunian V, Iijima KM, Schadt E, Brennand KJ, Zhang B. Transformative Network Modeling of Multi-omics Data Reveals Detailed Circuits, Key Regulators, and Potential Therapeutics for Alzheimer’s Disease. Neuron 2020, 109: 257-272.e14. PMID: 33238137, PMCID: PMC7855384, DOI: 10.1016/j.neuron.2020.11.002.Peer-Reviewed Original ResearchConceptsLate-onset Alzheimer's diseaseAlzheimer's diseaseKey regulatorPluripotent stem cell-derived neuronsRNAi-based knockdownStem cell-derived neuronsNovel therapeutic targetNext-generation therapeutic agentsCell-derived neuronsKey brain regionsIntegrative network analysisMulti-omics dataComplex molecular interactionsMulti-omics profilingNCH-51Neuronal impairmentGene subnetworksDisease-related processesCortical areasTherapeutic targetDrosophila modelNeuropathological phenotypeBrain regionsTherapeutic agentsMolecular mechanismsUtility of spontaneous animal models of Alzheimer’s disease in preclinical efficacy studies
Zeiss CJ. Utility of spontaneous animal models of Alzheimer’s disease in preclinical efficacy studies. Cell And Tissue Research 2020, 380: 273-286. PMID: 32337614, DOI: 10.1007/s00441-020-03198-6.Peer-Reviewed Original ResearchConceptsHuman Alzheimer's diseaseSpontaneous animal modelAlzheimer's diseaseAnimal modelsBiomarker progressionProgression of neuropathologyLate-onset Alzheimer's diseasePreclinical efficacy studiesHuman clinical trialsOnset Alzheimer's diseaseUsable outcome measuresAD-associated mutationsFamilial Alzheimer's diseaseNon-human primatesAmyloid neuropathologyInterventional studyClinical trialsSpontaneous modelHuman trialsOutcome measuresTherapeutic successPotential therapyNew therapiesRodent studiesEfficacy studies
2018
Alzheimer's Disease Risk Factor Pyk2 Mediates Amyloid-β-Induced Synaptic Dysfunction and Loss
Salazar SV, Cox TO, Lee S, Brody AH, Chyung AS, Haas LT, Strittmatter SM. Alzheimer's Disease Risk Factor Pyk2 Mediates Amyloid-β-Induced Synaptic Dysfunction and Loss. Journal Of Neuroscience 2018, 39: 758-772. PMID: 30518596, PMCID: PMC6343652, DOI: 10.1523/jneurosci.1873-18.2018.Peer-Reviewed Original ResearchConceptsTransgenic AD model miceAD model miceAbsence of Pyk2Synaptic dysfunctionModel miceHippocampal slicesSynaptic transmissionAlzheimer's diseaseAmyloid-β plaque pathologyHippocampal Schaffer collateral pathwayDisease riskLearning/memory deficitsDeletion of Pyk2Suppression of LTPBasal synaptic transmissionLate-onset Alzheimer's diseaseImpairment of learningSchaffer collateral pathwayAD-related synaptic dysfunctionAlzheimer's disease riskLate-onset Alzheimer's disease (LOAD) riskOnset Alzheimer's diseaseAge-dependent lossMechanism of actionSynaptic LTDAldehyde Dehydrogenases☆
Vasiliou V, Thompson D, Petersen D. Aldehyde Dehydrogenases☆. 2018, 146-163. DOI: 10.1016/b978-0-12-801238-3.99183-9.Peer-Reviewed Original ResearchAldehyde dehydrogenasesAldehyde dehydrogenase geneType II hyperprolinemiaTransgenic knockout mouse modelKnockout mouse modelHuman genomeHigh aldehyde dehydrogenase (ALDH) activityDehydrogenase geneExogenous aldehydesCancer stem cellsMolecular basisPhysiological processesDependent enzymesAldehyde dehydrogenase activityMicrophthalmia/anophthalmiaAldehyde dehydrogenaseStem cellsOxidative damageDehydrogenasesSjögren-Larsson syndromeGenesDehydrogenase activityLate-onset Alzheimer's diseasePivotal roleOxidation of aldehydes
2017
The aged rhesus macaque manifests Braak stage III/IV Alzheimer's‐like pathology
Paspalas CD, Carlyle BC, Leslie S, Preuss TM, Crimins JL, Huttner AJ, van Dyck C, Rosene DL, Nairn AC, Arnsten AFT. The aged rhesus macaque manifests Braak stage III/IV Alzheimer's‐like pathology. Alzheimer's & Dementia 2017, 14: 680-691. PMID: 29241829, PMCID: PMC6178089, DOI: 10.1016/j.jalz.2017.11.005.Peer-Reviewed Original ResearchConceptsLate-onset Alzheimer's diseaseCortical pathologyEntorhinal cortexAnimal modelsBraak stage III/IVAlzheimer's diseaseStage III/IVRhesus macaquesProgression of tauAlzheimer-like pathologyPrimary visual cortexSequence of tauDorsolateral prefrontal cortexTau pathologyPreventive strategiesAssociation cortexVisual cortexPrefrontal cortexCortexPathologyDiseaseOld animalsProtein kinase A (PKA) phosphorylationGenetic insultsMacaquesA Powerful Approach to Estimating Annotation-Stratified Genetic Covariance via GWAS Summary Statistics
Lu Q, Li B, Ou D, Erlendsdottir M, Powles RL, Jiang T, Hu Y, Chang D, Jin C, Dai W, He Q, Liu Z, Mukherjee S, Crane PK, Zhao H. A Powerful Approach to Estimating Annotation-Stratified Genetic Covariance via GWAS Summary Statistics. American Journal Of Human Genetics 2017, 101: 939-964. PMID: 29220677, PMCID: PMC5812911, DOI: 10.1016/j.ajhg.2017.11.001.Peer-Reviewed Original ResearchConceptsGWAS summary statisticsGenome-wide association studiesComplex traitsSingle nucleotide polymorphismsGenetic covarianceGenetic architectureLarge-scale genome-wide association studiesStrong genetic covarianceDistinct genetic architecturesSignificant genetic covarianceLate-onset Alzheimer's diseaseHigh minor allele frequencyGenetic profileFunctional genomeAmyotrophic lateral sclerosisMajor neurodegenerative diseasesMinor allele frequencyGenetic basisAssociation studiesTraitsLarge-scale inferenceSummary statisticsBiological interpretabilityAllele frequenciesNeurodegenerative diseasesMicroglia-Mediated Neuroprotection, TREM2, and Alzheimer’s Disease: Evidence From Optical Imaging
Condello C, Yuan P, Grutzendler J. Microglia-Mediated Neuroprotection, TREM2, and Alzheimer’s Disease: Evidence From Optical Imaging. Biological Psychiatry 2017, 83: 377-387. PMID: 29169609, PMCID: PMC5767550, DOI: 10.1016/j.biopsych.2017.10.007.Peer-Reviewed Original ResearchConceptsAlzheimer's diseasePlaque compactionAmyloid depositsInvolvement of microgliaPlaque-associated microgliaLate-onset Alzheimer's diseaseMyeloid cells 2Onset Alzheimer's diseaseMicroglia receptorMicroglia polarizationAD neuropathologyAxonal pathologyNeuroprotective functionDisease progressionOptical imaging studiesCurrent evidenceAD riskMicrogliaTherapeutic targetingAdjacent axonsImaging studiesCells 2DiseasePrecise mechanismRecent genetic studiesSystematic tissue-specific functional annotation of the human genome highlights immune-related DNA elements for late-onset Alzheimer’s disease
Lu Q, Powles RL, Abdallah S, Ou D, Wang Q, Hu Y, Lu Y, Liu W, Li B, Mukherjee S, Crane PK, Zhao H. Systematic tissue-specific functional annotation of the human genome highlights immune-related DNA elements for late-onset Alzheimer’s disease. PLOS Genetics 2017, 13: e1006933. PMID: 28742084, PMCID: PMC5546707, DOI: 10.1371/journal.pgen.1006933.Peer-Reviewed Original ResearchConceptsTissue typesNon-coding elementsNon-coding genomeComplex human diseasesLate-onset Alzheimer's diseaseIndividual cell typesRelevant tissue typesGWAS traitsTranscriptomic annotationGenome annotationFunctional annotationDNA elementsHeritability enrichmentHuman genomeLarge international consortiaVariety of cellsGenomeHuman diseasesAnnotation dataCell typesGenetic variantsOrgan system categoriesComplex diseasesSimilar localizationAnnotation
2016
O1‐03‐01: Integrative Analysis of Gwas Summary Data and Functional Annotations Highlights Signal Enrichment in Immune‐Related DNA Elements for Late‐Onset Alzheimer’s Disease
Lu Q, Mukherjee S, Crane P, Zhao H. O1‐03‐01: Integrative Analysis of Gwas Summary Data and Functional Annotations Highlights Signal Enrichment in Immune‐Related DNA Elements for Late‐Onset Alzheimer’s Disease. Alzheimer's & Dementia 2016, 12: p176-p177. DOI: 10.1016/j.jalz.2016.06.304.Peer-Reviewed Original Research
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