ArticleJournal of neuropathology and experimental neurology2020
Alzheimer Disease Pathology-Associated Polymorphism in a Complex Variable Number of Tandem Repeat Region Within the MUC6 Gene, Near the AP2A2 Gene.
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Article in Journal of neuropathology and experimental neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25citing papers in PubMed
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Who cites it
25 citing papers in PubMed, 32 citations in OpenAlex.
- Data-driven thresholds for standardized classification of severe Alzheimer's disease neuropathology using digital neuropathology.Brain pathology (Zurich, Switzerland) · 2026Article
- Comprehensive adjudication identifies 111 high-confidence loci for Alzheimer's disease and related dementias.medRxiv : the preprint server for health sciences · 2026Article
- Levetiracetam prevents Aβ production through SV2a-dependent modulation of APP processing in Alzheimer's disease models.Science translational medicine · 2026Article
- Alzheimer's disease: genetic background in the era of next-generation sequencing technologies.Brain communications · 2026Review
- Integrated phenotypic and proteomic screening identifies top-tier Alzheimer's disease therapeutic targets.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Integrated phenotypic and proteomic screening identifies top-tier Alzheimer's disease therapeutic targets.bioRxiv : the preprint server for biology · 2025Article
- [18F]flutemetamol uptake in the colon of a memory clinic population and its association with brain amyloidosis and the gut microbiota profile: an exploratory study.European journal of nuclear medicine and molecular imaging · 2025Article
- Analysis of targeted and whole genome sequencing of PacBio HiFi reads for a comprehensive genotyping of gene-proximal and phenotype-associated Variable Number Tandem Repeats.PLoS computational biology · 2025Article
- Whole Genome Variable Number Tandem Repeat Analysis in Alzheimer Disease.Neurology. Genetics · 2025Article
- A Mouse Model of Sporadic Alzheimer's Disease with Elements of Major Depression.Molecular neurobiology · 2025Article
- Integration of whole-exome sequencing and structural neuroimaging analysis in major depressive disorder: a joint study.Translational psychiatry · 2024Article
- In severe ADNC, hippocampi with comorbid LATE-NC and hippocampal sclerosis have substantially more astrocytosis than those with LATE-NC or hippocampal sclerosis alone.Journal of neuropathology and experimental neurology · 2023Article
- Frontotemporal neurofibrillary tangles and cerebrovascular lesions are associated with autism spectrum behaviors in late-life dementia.Journal of neurology · 2022Article
- Alpha adaptins show isoform-specific association with neurofibrillary tangles in Alzheimer's disease.Neuropathology and applied neurobiology · 2022Article
- Advancing genomic technologies and clinical awareness accelerates discovery of disease-associated tandem repeat sequences.Genome research · 2022Review
- Role of adaptin protein complexes in intracellular trafficking and their impact on diseases.Bioengineered · 2021Article
- Straglr: discovering and genotyping tandem repeat expansions using whole genome long-read sequences.Genome biology · 2021Article
- Mutant Presenilin 1 Dysregulates Exosomal Proteome Cargo Produced by Human-Induced Pluripotent Stem Cell Neurons.ACS omega · 2021Article
- Genome-wide characterization of human minisatellite VNTRs: population-specific alleles and gene expression differences.Nucleic acids research · 2021Article
- Searching the Dark Genome for Alzheimer's Disease Risk Variants.Brain sciences · 2021Review
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Authors and funding
21 authors at 2 institutions in 1 country.
Yuriko KatsumataSanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky.
David W FardoSanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky.
Adam D BachstetterSanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky.
Sergey C ArtiushinSanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky.
Wang-Xia WangSanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky.
Angela WeiSanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky.
Lena J BrzezinskiSanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky.
Bela G NelsonSanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky.
Qingwei HuangSanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky.
Erin L AbnerSanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky.
Sonya AndersonSanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky.
Indumati PatelSanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky.
Benjamin C ShawSanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky.
Douglas A PriceSanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky.
Dana M NiedowiczSanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky.
Donna W WilcockSanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky.
Gregory A JichaSanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky.
Janna H NeltnerSanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky.
Linda J Van EldikSanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky.
Steven EstusSanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky.
Peter T NelsonSanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky.
Cancer Research And Biostatistics · USUniversity of Kentucky · US
Funding
Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6MLarge Scale Genome SequencingU54HG003079 · NHGRI · WASHINGTON UNIVERSITY · PI DUTCHER, SUSAN K · 2004 to 2016
$445.7MThe Human Genome Sequencing CenterU54HG003273 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI GIBBS, RICHARD A · 2004 to 2015
$341.3MNational Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8MNATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8MARIC Neurocognitive Study (ARIC-NCS) Renewal 2023-2028U01HL096812 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI JOSEF CORESH, THOMAS H MOSLEY · 2010 to 2026
$65.7MAlzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4MTHE NIA GENETICS OF ALZHEIMER'S DISEASE DATA STORAGE SITEU24AG041689 · NIA · UNIVERSITY OF PENNSYLVANIA · PI LI-SAN WANG · 2012 to 2026
$42.3MWhole Genome Sequencing in Ethnically Diverse Cohorts for the ADSP Follow-Up Study (FUS)U01AG057659 · NIA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI MAYEUX, RICHARD P, PERICAK-VANCE, MARGARET A. · 2017 to 2021
$34.4MGenome Center for Alzheimer's Disease (GCAD)U54AG052427 · NIA · UNIVERSITY OF PENNSYLVANIA · PI WANG, LI-SAN · 2016 to 2025
$32.8MBuilding on GWAS for NHLBI-disease: the CHARGE consortiumRC2HL102419 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI BOERWINKLE, ERIC A. · 2009 to 2010
$27.6MUniversity of Kentucky Alzheimer's Disease Research CenterP30AG072946 · NIA · UNIVERSITY OF KENTUCKY · PI LINDA J VAN ELDIK · 2021 to 2026
$23.5MNCRR NIH HHS S10 RR026489NHGRI NIH HHS U54 HG003067NHGRI NIH HHS U54 HG003079NHGRI NIH HHS U54 HG003273NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201100005CNHLBI NIH HHS HHSN268201100005GNHLBI NIH HHS HHSN268201100005INHLBI NIH HHS HHSN268201100006CNHLBI NIH HHS HHSN268201100007CNHLBI NIH HHS HHSN268201100007INHLBI NIH HHS HHSN268201100008CNHLBI NIH HHS HHSN268201100008INHLBI NIH HHS HHSN268201100009CNHLBI NIH HHS HHSN268201100009INHLBI NIH HHS HHSN268201100010CNHLBI NIH HHS HHSN268201100011CNHLBI NIH HHS HHSN268201100011INHLBI NIH HHS HHSN268201100012CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HHSN268201500001CNHLBI NIH HHS HHSN268201500001INHLBI NIH HHS N01 HC025195NHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085086NHLBI NIH HHS R01 HL070825NHLBI NIH HHS R01 HL105756NHLBI NIH HHS RC2 HL102419NHLBI NIH HHS U01 HL080295NHLBI NIH HHS U01 HL096812NHLBI NIH HHS U01 HL096814NHLBI NIH HHS U01 HL096899NHLBI NIH HHS U01 HL096902NHLBI NIH HHS U01 HL096917NHLBI NIH HHS U01 HL130114NIA NIH HHS P30 AG028383NIA NIH HHS P30 AG072946NIA NIH HHS R01 AG015928NIA NIH HHS R01 AG020098NIA NIH HHS R01 AG023629NIA NIH HHS R01 AG033040NIA NIH HHS R01 AG033193NIA NIH HHS R01 AG042475NIA NIH HHS R01 AG049607NIA NIH HHS R01 AG054076NIA NIH HHS R01 AG057187NIA NIH HHS R01 AG061111NIA NIH HHS R21 AG050146NIA NIH HHS R21 AG061551NIA NIH HHS R56 AG057191NIA NIH HHS U01 AG016976NIA NIH HHS U01 AG032984NIA NIH HHS U01 AG049505NIA NIH HHS U01 AG049506NIA NIH HHS U01 AG049507NIA NIH HHS U01 AG049508NIA NIH HHS U01 AG052409NIA NIH HHS U01 AG052410NIA NIH HHS U01 AG052411NIA NIH HHS U01 AG057659NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG041689NIA NIH HHS U54 AG052427NIA NIH HHS UF1 AG047133NINDS NIH HHS R01 NS017950
Abstract
We found evidence of late-onset Alzheimer disease (LOAD)-associated genetic polymorphism within an exon of Mucin 6 (MUC6) and immediately downstream from another gene: Adaptor Related Protein Complex 2 Subunit Alpha 2 (AP2A2). PCR analyses on genomic DNA samples confirmed that the size of the MUC6 variable number tandem repeat (VNTR) region was highly polymorphic. In a cohort of autopsied subjects with quantitative digital pathology data (n = 119), the size of the polymorphic region was associated with the severity of pTau pathology in neocortex. In a separate replication cohort of autopsied subjects (n = 173), more pTau pathology was again observed in subjects with longer VNTR regions (p = 0.031). Unlike MUC6, AP2A2 is highly expressed in human brain. AP2A2 expression was lower in a subset analysis of brain samples from persons with longer versus shorter VNTR regions (p = 0.014 normalizing with AP2B1 expression). Double-label immunofluorescence studies showed that AP2A2 protein often colocalized with neurofibrillary tangles in LOAD but was not colocalized with pTau proteinopathy in progressive supranuclear palsy, or with TDP-43 proteinopathy. In summary, polymorphism in a repeat-rich region near AP2A2 was associated with neocortical pTau proteinopathy (because of the unique repeats, prior genome-wide association studies were probably unable to detect this association), and AP2A2 was often colocalized with neurofibrillary tangles in LOAD.
Indexed as
Adaptor Protein Complex 2Adaptor Protein Complex alpha SubunitsAgedAged, 80 and overAlzheimer DiseaseAutopsyCohort StudiesFemaleGenome-Wide Association StudyGenotypeHumansMaleMinisatellite RepeatsMucin-6Neurofibrillary TanglesPolymorphism, GeneticAdaptor Protein Complex 2adaptor protein complex 2, alpha 2 subunitAdaptor Protein Complex alpha SubunitsMUC6 protein, humanMucin-6ADSPAP-2Digital pathologyGWASScanScopeWhole-exome sequencing
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