editFirst AuthorCollaboratorsLast AuthorManuscript TitleTarget JournalTarget Submission DateManuscript StatusGrantAimBrief Description of Goals

YouCruchaga, HarariKarchMS4A4A modifies the risk of Alzheimer?s disease and relates cholesterol metabolism and immune responseNature NeuroscienceSpring 2022In PrepADRCBiomarker Aim 3

to define the impact of a novel regulator of strem2 and ad risk/resilience gene on ad pathogenesis and microglia function

XiongACS and DIANReady to submit as soon as the DIAN-ADNI ms is submitted

Xiongbiomarker comparisons between ACS and DIANready to submitACS

Xiongbiomarker harmonization across labs/ lots/scanners/softwareongoingADRC/HASD/ACS

XiongCross sectional and longitudinal relationship between WMH and AD biomarkers and cognition1st draft almost ready to shareADRC/HASD/ACS

Xiongcrosss ectional and longitudinal racial and sex differences in AD biomarkersongoingADRC/HASD/ACS/R01

XiongData from his R01 to justify enrolling people in their 30sCo-author review

XiongYr 1 biomarker predict Yr 10 cognitionongoingADRC/HASD/ACS

WischCruchagaAncesUnsupervised clustering of AT(N) progression + Supervised clustering of proteomics dataTranslational NeurodegenerationApril.2022Manuscript: under review?

identify underlying proteome expression associated with various AT(N) classifications

WischAncesSchindlerPrediction of regional amyloid PET SUVR by plasma and CSF Ab42/Ab40A&DJune.2022Manuscript being draftedACSP1 Aim 1 – P2 Aim 3

To determine the relationship between plasma Ab42/Ab40, CSF Ab42/Ab40, and amyloid PET

Wang, QSchindlerBenzingerEarly Hindered Water Diffusion Alternation in White Matter is associated with Beta-amyloid and Predicts cognitive decline in ADBrainJune.2022Manuscript: in preparationACSP1 Aim3

to quantify the extracellular water in preclinical and early symptomatic AD and investigate its association with cognitive measures

Wang, QBenzingerWang, Y.Quantification of neuroinflammation using diffusion MRI and PETAlzheimer&dementiaOct.2022Analyses: in progressHASDE Aim 3

to validate diffusion MRI quantified neuroinflammation with PET PK11195.?

Wang, L.Western?AncesCruchaga, SungProteomic profiling identified plasma biomarkers for SARS-CoV-2 infection and severity of COVID-19 patientsscience translation medicineMay . 2022In preparationADRC; HASDGenetics Core Aim X; P3 Aim 4

Examining COVID 19 in plasma biomarkers with patients with AD

Wang, LBenzingerCorrelation of PiB PET with autopsy resultsManuscript: circulating (mentor-author)ACS & ADRCACS: P1 Aim1 & ADRC: D Aim 2, ADRC F Aim 3

TimsinaCruchagaComparative analysis of Alzheimer?s disease Cerebrospinal fluid biomarkers measurement by multiplex SOMAscan platform and immunoassay-based approachA&DApril.2022SubmittedACSCore C Aim 3

The goal of this project is to access the performance of SOMAscan ?based protein measurement in comparison to immunoassays based protein measures for CSF biomarkers in AD.

SungCruchagaMulti-tissue proteomics identifies molecular signatures for sporadic and genetically defined Alzheimer disease casesNature NeuroscienceUnder Review

StrainAvi, Benzinger, GordonAncesADAD vs LOAD for resting state functional connectivityNeuroimageUnder revisionACSP1 Aim 3

Comparison of ADAD LOAD across the disease spectrum with FC and PCA based approach

StrainAncesComparison of DTI and resting state measuresACSP1 Aim 3

StrainChia-LingLongitudinal WMH in ADRC with WLMANature NeuroscienceJune.2022Manuscript editsACSP1 Aim 3

Novel way to evaluate longitudinal expansion of WMH in association with AD disease progression

StrainAncesWhite matter hyperintensities in ADRCBrainAug.2022Manuscript writingACSP1 Aim 3

Finalizing results ; Using semiautomated program relate WMH to biomarkers and cognition

SchindlerLi, Y.BatemanConcordance of plasma Ab42/Ab40, CSF Ab42/Ab40 and amyloid PETNature MedicineAnalyses: in progressACSP1 Aim 1 – P2 Aim 3

To evaluate the temporal ordering of plasma Ab42/Ab40, CSF Ab42, and amyloid PET

SchindlerBarthelemyBatemanUsing phophorylated CSF pTau as a clock for preclinical ADJAMA NeurolAnalyses underwayHASD; Schindler R01P1 Aim 1

To use CSF pTau species to stage preclinical AD

RoseneCruchaga, Harari, Holtzman, Cirrito, LeeKarchPhospholipase D3 contributes to Alzheimer?s disease risk via disruption of A? clearance and microglia response to amyloid plaquesSci Trans MedSubmitted Jan.2022In RevisionADRCBiomarker Core Aim 3

define the impact of a novel ad risk gene in AD pathogenesis

RoseneKarchVascular contribution of PLD3 to Alzheimer diseaseTBDWinter 2022In PrepADRCBiomarker Core Aim 3

define the impact of a novel ad risk gene in AD pathogenesis and vascular pathology

RonJohntestest testtest

RajiQ WangBenzingerDBSI obesity ADRC controlsACSP1 Aim 3

RahmaniBenzingerIntracranial internal carotid artery calcification is not predictive of future cognitive declineAlz Res TherapyManuscript: PublishedACSP1 Aim 3 and P2 Aim 1

RahmaniFriedrichsenBenzingerSIEMENS TeamPlay vs. FS 7.1 volumetric comparisonAnalyses: in progressACSP1 Aim 3

RahmaniRajiBMI Connectome with Dr. RajiJADManuscript: revising or responding to reviews

RahmaniRaji, BenzingerBMI / EDI with Dr. RajiManuscript: conceptual stageACSP1 Aim 3

NovotnyHarariMetabolomic and lipidomic signatures in autosomal dominant and late-onset Alzheimer disease brainsAlz and DemMay.2022SubmittedADRC/HASDP3 Aim 4; Core D Aims 2, 3

Identify altered metabolomic reading and patways in LOAD, ADAD

NicosiaAschenbrenner, Balota, Sliwinski, Tahan, Adams, Stout, Wilks, Gordon, Benzinger, Fagan, Xiong, Bateman, MorrisHassenstabUnsupervised high-frequency smartphone-based cognitive assessments are reliable, valid, and feasible in older adults at risk for Alzheimer diseaseJournal of the International Neuropsychological SocietyUnder ReviewProject 4Aim 1

Examine reliability, validity, and feasibility in ARC

MinayaCruchaga, HarariKarchConserved disease signatures shared among MAPT mutations reveals defects in calcium signalingMolecular NeurogenerationSpring 2022In PrepADRCBiomarker Core Aim 3

to identify targetable pathways that are commonly changed across tau mutations

MinayaYooKarchDirectly reprogrammed neurons capture molecular signatures of FTLD-tauMolecular PsychiatryFall 2022In PrepADRCBiomarker Core Aim 3

to use multiple in vitro human cell systems to develop predictive models of moelcular signatures of disease

MillarLuckettAncesFC Predicted Brain Age and AD MeasurementsNeuroImagepublishedProof in CorrectionACSP1 Aim 3

Develop models of functional connectivity based “brain age” and test differences in symptomatic and preclinical AD

MillarLuckettAncesMultimodal predicted brain age, AD biomarkers, and cognitionNeurobiology of AgingJune.2022Manuscript: in preparationACSP1 Aim 3

Develop models of “brain age” based on functional and structural MRI. Test relationships with AD biomarkers and cognition

MillarBenzinger, Wheelock… Strain,Ances, GordonFC network driven tau spreading in group and individual connectomesBrainSept.2022Performing analysesACSP1 Aim 2

Model tau PET spreading through FC brain networks. Compare group average to subgroup-specific to individual network models.

Meeker, MillarAncesBOLD variability in relation to graph theory measuresAnalyses: in progressACSP1 Aim3

Meeker, LuckettGordon, SchindlerAncesBiomarker clustering in ADRCData request submitted

Meeker, LuckettBalotaAncesParcelltion projectData: processing?

MeekerLuckett, Ances, SchindlerGordonInterrelationships and and the structure between biomarkers.Analyses in processACS/HASD/ ADRC

MeekerBalls-Berry, Babulal, GordonAncesEthno-racial differences in MRI/biomarker heterogeneity profilesWriting up data request; proposal sent out for ADRC REC component -> will be used for K submission

MeekerAncesGraph theory in resting state of ADRCMs written and should be sent to authors

MeekerAncesPtau site relationships with RS-FC and PETData request submitted (finishing same project in DIAN)

MeekerAncesPtau sites and resting state fmriAnalyses: completedACSP1 Aim3

MeekerGordon, BenzingerAncesRace differernces in rs-fcAnnals of NeurologyManuscript: re-submittedACSP1 Aim3

MeekerAncesResting state and polygenetic risk scoreManuscript: in preparationACS & ADRCACS: P1 Aim 3, ADRC: G Aim 3

MeekerGordonAncesTREM2/MS4A4A in relation to imaging biomarkers and cognitionproposal/grant: in preparationACSP1 Aim 1 and P2 Aim 3

writing proposal for Charleston conference ;

MeekerGraph theory in resting state of ADRC and DIANManuscript: in preparationACSP1 Aim3

MeekerLuckett, C. ChenNFL and Resting stateData: requested or need data from other core/centersACSP1 Aim 3 and P2 Aim 3

MeekerGordon, WischResting state and graph theory and CSF measuresData: requested or need data from other core/centersACSP1 Aim 3 and P2 Aim 1

MeekerAncesCSF NFL as a funciton of age and AT(N) measures as well as amyloidManuscript: in preparationACSP1 Aim 1 and P2 Aim 3

McKay, KoenigBenzingerWMH Patterns in Preclinical ADNeuroimageNov.2022Manuscript: in preparationACSP1 Aim3

Patterns of white matter hyperintensities in preclinical AD

McKay, HobbsDayGordonLifestyle factors (and BMI over time) ADRC/DIAN/ADNIAlzheimer Disease: Diagnosis, Assessment? and Disease MonitoringAug.2022Analyses: in progressACSP1 Aim 3

Looking at the impact of lifestyle factors such as BMI, and whether the obesity paradox is present across three AD-related cohorts.?

McKay, HobbsDoering, BenzingerGordonAPOE: Comparison of ADAD and sporadic AD (ADNI, ADRC, DIAN)Neuroimage: clinicalAug.2022Manuscript: in preparationACSP1 Aim 3 and P2 Aim 1

Comparison of the impact of APOE genotype on biomarkers of AD within sporadic and ADAD cohorts

McKayGordon, Raji, Hobbs, RahmaniBenzingerEdge Density and Cognition (and NfL) in DIAN and sporadic ADNeuroimageJan.2023Data: processingACSP1 Aim 3 and P2 Aim 3

Validating a novel white matter metric of connectivity for understanding breakdown of pathways in preclinical AD.

McKayHobbs, Millar, BenzingerGordonCognitive control and DTIBiological PsychologyJune.2022Manuscript: ready to be submittedACSP1 Aim 3

How does cognitive status moderate the relationship between white matter integrity and attentional control metrics.?

McKayAschenbrenner, Millar, NicosiaHassenstabData driven composites of cognition within aging researchAlz & DementiaJune.2022Analyses: in progressACSP1 Aim 3 and P2 Aim 1

Comparing the Knight ADRC PACC, ADCS PACC, and domain-specific composites derived from the ADRC data.?

MassoumzadehGordon, Chen, Schindler, Friedrichsen, MorrisBenzinger, XiongBMI and risk of Dementia in ADRC/ADNI/AIBL/HABA/WRAP/Racial disparity (RD)Manuscript: conceptual stageACSP1 Aim 3

MassoumzadehGordon, Chen, Schindler, Friedrichsen, MorrisBenzinger, XiongPhysical Activity and risk of Dementia in ADRC/ADNI/AIBL/HABA/WRAP/RDManuscript: conceptual stageACSP1 Aim 3 & P4 Aim 1

MassoumzadehGordon, Chen, Schindler, Friedrichsen, MorrisBenzinger, XiongRace and risk of Dementia in ADRC/ADNI/AIBL/HABA/WRAP/RDManuscript: conceptual stageACS & HASDP1 Aim 3 & HASD P1 Aim 1

MassoumzadehGordon, Chen, Schindler, Friedrichsen, MorrisBenzinger, XiongSex and risk of Dementia in ADRC/ADNI/AIBL/HABA/WRAP/RDManuscript: conceptual stageACSP1 Aim 3

MarshCruchaga, MorrisKarchSomatic and Stem Cell Resource for Studying the Genetic Architecture of Neurodegenerative DiseaseStem Cell ReportsSummer 2022In PrepADRCBiomarker Aim 2

Stem cell resource paper

MahaliHarariKarchDefective proteostasis in induced pluripotent stem cell models of frontotemporal lobar degenerationTranslational PsychiatrySpring 2022In RevisionADRCBiomarker Aim 3

to define the impact of tau mutation on proteostasis

MahaliKarchDefective proteostasis in patient-derived iPSC-astrocytes and neurons carrying a MAPT IVS10+16 mutationAging CellSummer 2022In PrepADRCBiomarker Aim 3

to define the impact of splicing mutation in tau on cellular homeostasis across CNS cell types

Luckett McCulloughMachine learning in DIAN and ADRCManuscript being written

LuckettAncesMachine learning comparison between ADAD and LOADAnalyses: in progress??

LuckettPatrick/CharlieAnces, GordonExamine temporal ordering of biomarkers, hierarchical clustering based upon individual differences, and sping embedded analysis of all biomarkers for DIANActa NeuropathologicaAnalyses: in progressACSP1 Aim 2

LuceyLongitudinal AD biomarkers predict sleep disturbancesAnalyses on goingHASD P21

LuceyMignotOrexin, sleep, and AD biomarkersCSF orexin-A measurements completed in the Mignot; waiting to receive the dataHASD P22

LongXiong? HoltzmanMorrisPreclinical Alzheimer’s Disease Biomarkers Accurately Predict Cognitive and Neuropathological OutcomesBrainSpring 2022Submitted and returned for revisions

To validate the use of CSF and amyloid PET biomarkers for detection of preclinical AD against neuropath dx

KoppisettiBateman, SatoKarchImpact of development on tau proteoform kinetics in human iPSC derived cerebral organoidseLifeSpring 2022In PrepADRCBiomarker Aim 3

To understand how age and genotype impact tau kinetics in organoids

JindalFriedrichsen, Rahmani, C. Chen, LaurenBenzingerBaseline Prevalence of Amyloid-Related Imaging Abnormalities in Early ADAJRManuscript: in preparation

Abstract accepted at ARRS 2022

HorieBateman,Perrin, GhoshalSatoCSF tau microtubule binding region identifies pathological changes in primary tauopathiesNature MedicineMay.2022In PrepADRC

To profile CSF tau in non-AD tauopathy

GordonBenzingerMultimodal comparisons of amyloid (PET CSF AB42/AB40), tau (PET and ptau181), and neurodegeneration (MRI and NfL)unsureunsureManuscript: in preparationACSP1 Aim 1 and P2 Aim 3

How do CSF/plasma levels of NfL and tau relate to one another. Is this relationship mediated through volume?

GordonTau binding in PARTunsureMarch. 2022Manuscript: submittedACSP1 Aim 1 and 2

Under Review

FriedrichsenBenzingerProtein expression levels related with MCH in DIAD [and LOAD]Manuscript: conceptual stageACSP1 Aim 3

FloresSu, Nickels, Schwarz, McConathyGordonTau PET off-target bindingJournal of Nuclear MedicineFeb. 2022Manuscript: under revisionACSP1 Aim 2

This project aims to examine the influence skull signal may have on quantitative PET analyses using 18F-flortaucpir. Additionally, we determine whether this skull signal can explain some of the sex differences observed in tau PET in the ACS cohort.

FilipelloPiccio, Cruchaga, HarariKarchDefect in lysosomal activity and lipid metabolism in TREM2 mutationsJCISpring 2022In PrepADRCBiomarker Aim 3

To define the impact of TREM2 mutations in stem cell and brains

EteleebHarariMulti-omic subtyping of Alzheimer Disease reveals Alpha-Syn dysregulation associated with worse clinical outcomesNeuronApr. 2022Writing the manuscriptHASDP3 Aim3

Leverage Machine Learning and multiple modalities of omics to determine molecular subtypes of AD

DoeringGordon, Xiong, CobleBenzingerAmyloid PET Tracer Longitudinal ComparisonunsureunsureAnalyses: in progressACSP1 Aim 1

We will evaluate the stability of AV45 and PiB amyloid PET tracers for longitudinal analyses using an ICC analysis. We will then create a model for adjusting SUVRs of each tracer when running analyses using longitudinal data with both tracers.

DoeringMcCullough, GordonBenzingerTau PET spread (surface maps and tau spatial spread)unsureunsureManuscript: in preparationACSP1 Aim 2

We will use changepoint models to estimate a dynamic temporal ordering of all of the longitudinal biomarker data collected in the ACS program project grant. This will include a global cognitive composite and domain specific cognitive composites from the Clinical Core, CSF biomarkers from Project 2/Biomaker Core of the ACS, (Grant P01AG026276) in combination with the imaging change points in Aim 2b.

DincerChen, McKayGordonEffect of APOE genotype on tau not mediated by amyloidManuscript: revising or responding to reviewsACSP1 Aim 3

DincerLOAD and DIAN cortical signature MapsAnalyses done; MS being written.

D’Oliveira AlbanusKarch, Benitez, Cruchaga?Morris, BatemanHarariCharacterizing Disrupted Cellular Crosstalk Signaling Networks in Alzheimer?s Disease Using Single-Nuclei TranscriptomicsNeuronJuly.2022Analyses close to finishedHASD/ADRCHASD P3 Aim 4; ADRC Core D Aim 2, Core F Aim 3, Core G Aims 2 &5

Determine the cellular cross-talk dysregulation involving AD genes identified in Genetic Analyses

Cummings-VaughnBalls-BerryMorrisThe Impact of Ethnoracial Factors on Reported Memory Problems – In draftNeuro. Journal of Americans Geriatrics SocietyApril.2022Last draftHASDP1 Aim 4

Evaluate the risk of progression to clinically significant cognitive impairment and relative relationship of race and ethnicity with respect to memory problems in individuals with self-reported and collateral source?reported memory problems

Chen, C., PonisioLang, Flores, Schnidler, Fagan, MorrisBenzingerComparing tau PET visual interpretation with tau PET SUVR and CSF phosphorylated tauJNMMar.2022Under reviewHASD/ACSHASD P1 Aim 1; ACS P1 Aim 3

Compare tau PET visual interpretation with tau PET SUVR and CSF p-tau181

Chen, C.Guo, Li, … Ances, MorrisBenzingerAutoradiographic characterization of frontal lobe Alzheimer disease neuropathologic change with translocator protein, tau, and amyloid-? receptor bindingACTNunsureCirculated to co-authorsADRCNeuropath Core Aim 2

Compare TSPO, tau, and A? autoradiography

Chen, C.Schultz, Luckett, Friedrichsen? AncesBenzingerRoles of neuronal injury and loss in imaging-fluid Alzheimer disease biomarker discordances under the Amyloid/Tau/Neurodegeneration frameworkMolecular PsychiatryunsureCirculated to co-authors; needs revisionsACSP2 Aim 3

Compare synaptic, neuronal, and neuroinflammatory biomarkers with A?, tau, and neurodegeneration biomarkers

Chen, C.Feldman, Dincer, Flores?MorrisBenzingerFreeSurfer segmentation consistency versus efficency in studies of memory and agingFrontiersunsureCirculated to co-authors; needs revisionsHASDImaging Core Aim 3

Compare FreeSurfer software versions and workflows

Chen, C.Gordon, McCullough? MorrisBenzingerDetecting tau PET positivity in AD without a priori assumptions about its frequencyBrainunsureRejected by Brain; needs revisionsHASDImaging Core Aim 3

Compare tau PET positivity models

Chen, A., McKayGordon, Friedrichsen, Massoumzadeh,BenzingerLongitudinal mri Predicting cognitive decline: hippocampus volume and cortical thickness, longitudinalNeuroimagingMay.2022Manuscript: ready to be submittedACS & HASDP1 Aim 1

Abstract accepted AAIC2020 – revise (two manuscript to be submitted) ; Using Oasis data, compare the relationship between baseline amyloid and rate of change and cognition

Chen, ABrier, GordonBenzingerGraph theory in tau PET and PiB PET of OasisBrain ConnectivityAug.2022Manuscript: in preparationACSP1 Aim 1

Abstract accepted AAIC2021

Chen, ACruchaga, GordonBenzingerGWAS and Candidate gene association analysisJADDec.2022Analyses: in progressHASDP3 Aims 3 and 4

Abstract to be submitted to AAIC2022 and AARF-grant submitted Fall 2021

BraseKarch, Benitez, CruchagaHarariA landscape of the genetic and cellular heterogeneity in Alzheimer diseaseNat Neuro44576Manuscript: submittedADRCGenetics Aim 5

Investgate the pathways and molecular networks antered in ADAD and LOAD

BraseHohmanHarariThe sex-specific effects of KDM6A expression is microgliaScience Translational MedicineAug. 2022Analyses ongoingADRCGenetics Aim 5

Determine the brain cell type specific patterns of expression of KDM6A, and X-linked gene that avoids X-inactivation and associated with sex-related differences in AD

BoerwinkleFlores, Chen, Gordon, BenzingerAncesComparison of neuroimaging measures between ADAD and DSLancet NeurologyJan. 2022Manuscript: circulating to co-authorsACSP1 Aim 1

BhagatCruchaga, HarariKarchRole for long non-coding RNAs in tauopathyScience AdvancesFall 2022In PrepADRCBiomarker Aim 3

To define the impact of non coding RNAs on tauopathy

BarthelemyBateman, Gordon, LiSchindlerCorrelation between CSF pTau isoforms, amyloid PET, tau PET, and CSF Ab42/Ab40Lancet NeurologyMid May 2022Analyses in progressSchindler RO1; Barthelemy ADRC Dev ProjectP1 Aim 1; P2 Aim 1 and 2

Determine which pTau isoforms are best correlated with amyloid PET, tau PET, CSF Ab42/Ab40, and structural MRI volumes

Balls-Berry, StreitzXiongMorrisExploring Social and Structural Determinants of Health of Older Adults: A Preliminary Survey – Concept

Balls-BerryBabulalMorrisHealth Disparities in Dementia – Waiting on proofs

Balls-BerryDenny, Johnson, MoulderMorrisLessons Learned from Alzheimer Disease Research Center: Creating a Health Disparities and Equity Core – Concept

AschenbrennerDlaminiSchindlerCognitive decline as predicted by CSF tau isoforms and emerging CSF biomarkers (Ng, SNAP-25, VILIP-1, YKL-40, NfL)BrainProject just startedAnalyses startingSchindler R01, ACS Project 2P2 Aim 3

Compare prediction of cognitive decline by CSF ptau isoforms and emerging CSF biomarkers

AschenbrennerHassenstabSchindlerCognitive decline as predicted by plasma and CSF Ab42/Ab40 and NfLAnnals of NeurologyApr. 2022Ready to submitSchindler R01P2 Aim 3

Compare prediction of cognitive decline by CSF and plasma Ab42/Ab40 and NfL

AliSung, Morris, Fagan, PerrinCruchagaLeveraging large multi-center cohorts of Alzheimer Disease endophenotypes to understand the role of Klotho heterozygosity on disease riskPloSOneMarch. 2022Under RevisionHASDP3 Aim 1

Determine if Klotho heterozygosity (KL-VSHET+) is associated with reduced AD risk and ?-amyloid (A?) pathology in individuals who carry APOE4.