ArticleJournal of neuropathology and experimental neurology2021
Early Selective Vulnerability of the CA2 Hippocampal Subfield in Primary Age-Related Tauopathy.
Erratum issuedOpen access · bronzeAbstract read
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Article in Journal of neuropathology and experimental neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 55 papers.
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55citing papers in PubMed
4.2field-weighted citation impact, top 5% of its field
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Who cites it
55 citing papers in PubMed, 66 citations in OpenAlex.
- Activated microglial phenotypes in the hippocampal CA2 subfield are implicated in Lewy body disease progression.Acta neuropathologica · 2026Article
- Cortical subpial aging-related tau astrogliopathy in older adult men who participated in youth amateur American-style football.Journal of neuropathology and experimental neurology · 2026Article
- Proteomic comparison of hippocampal neurofibrillary tangles in PART, intermediate Alzheimer's disease and advanced Alzheimer's disease.Acta neuropathologica · 2026Article
- Amyloid plaques associated with shift in patterns of hippocampal tau pathology in middle age.Journal of Alzheimer's disease : JAD · 2026Article
- A novel hierarchical framework elucidating regional differences in α-synuclein and tau co-pathology in military veterans with parkinsonism.Journal of neuropathology and experimental neurology · 2026Article
- Neocortical tau burden determines the degree of cognitive impairment in individuals with Braak stage V neurofibrillary degeneration.Acta neuropathologica · 2026Article
- Hippocampal subfield thickness and shape analysis in examining the impact of TDP-43 in primary age-related tauopathy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Microglial reactivity in the hippocampal CA2 is associated with advanced neuronal α-synucleinopathy.bioRxiv : the preprint server for biology · 2026Article
- Proteomic remodelling of the neurofibrillary tangle from "PART" to advanced Alzheimer's disease.Research square · 2026Article
- Longitudinal assessment of cognitive decline and resilience in high-level Alzheimer disease neuropathologic change.Alzheimer's research & therapy · 2025Article
- Primary age-related tauopathy.Acta neuropathologica · 2025Review
- Alcohol consumption in P301S mice accelerates gait impairments, modifies aggregation of pathological tau and alters microglia within the hippocampus.Alcohol, clinical & experimental research · 2025Article
- Reply: PART and amyloid cascade hypotheses are alive and well (but are not so simple).Acta neuropathologica · 2025Article
- Hippocampal tau distribution in primary age-related tauopathy: The Vantaa 85+ Study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- An integrated view of the relationships between amyloid, tau, and inflammatory pathophysiology in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Cognitive and neuropsychological trajectories in patients with mixed neurodegenerative pathologies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Cognitive decline in community-dwelling older persons with primary age-related tauopathy: role of anatomical location of tangles and other co-existing brain pathologies.Acta neuropathologica · 2025Article
- PRMT3-Mediated H4R3me2a Promotes Primary Age-Related Tauopathy by Driving Tau Hyperphosphorylation in Neuron.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Insights into pathophysiology, biomarkers, and therapeutics in tauopathies: Proceedings of the Tau2024 Global Conference.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Transcriptional signatures of hippocampal tau pathology in primary age-related tauopathy and Alzheimer's disease.Cell reports · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
57 authors at 20 institutions in 5 countries.
Jamie M WalkerFrom the Department of Pathology, University of Texas Health Science Center, San Antonio, Texas, USA.
Timothy E RichardsonFrom the Department of Pathology, University of Texas Health Science Center, San Antonio, Texas, USA.
Kurt FarrellDepartment of Pathology and Nash Family Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Megan A IidaDepartment of Pathology and Nash Family Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Chan FoongDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Ping ShangDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Johannes AttemsInstitute for Ageing and Health, Newcastle University, Newcastle upon Tyne, United Kingdom.
Gai AyalonDepartment of Neuroscience, Genentech Inc., South San Francisco, California, USA.
Thomas G BeachNeuropathology, Banner Sun Health Research Institute, Sun City, Arizona, USA.
Eileen H BigioDepartment of Pathology, Northwestern Cognitive Neurology and Alzheimer Disease Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Andrew BudsonDepartment of Pathology, VA Medical Center & Boston University School of Medicine, Boston, Massachusetts, USA.
Nigel J CairnsDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
María CorradaInstitute for Memory Impairments and Neurological Disorders, UC Irvine, Irvine, California, USA.
Etty CortesDepartment of Pathology and Nash Family Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Dennis W DicksonDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Peter FischerDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Laboratory Medicine Program, University Health Network, and Tanz Centre for Research in Neurodegenerative Disease, Krembil Brain Institute, Toronto, Ontario, Canada.
Margaret E FlanaganDepartment of Pathology, Northwestern Cognitive Neurology and Alzheimer Disease Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Erin FranklinDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
Marla GearingDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
Jonathan GlassDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
Lawrence A HansenDepartments of Neurosciences and Pathology, University of California, San Diego, La Jolla, California, USA.
Vahram HaroutunianDepartment of Psychiatry and Alzheimer's Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Patrick R HofDepartment of Pathology and Nash Family Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Lawrence HonigDepartment of Neurology, Columbia University Irving Medical Center, New York, New York, USA.
Claudia KawasInstitute for Memory Impairments and Neurological Disorders, UC Irvine, Irvine, California, USA.
C Dirk KeeneDepartment of Pathology, University of Washington, Seattle, Washington, USA.
Julia KoflerDepartment of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Gabor G KovacsDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Laboratory Medicine Program, University Health Network, and Tanz Centre for Research in Neurodegenerative Disease, Krembil Brain Institute, Toronto, Ontario, Canada.
Edward B LeeCenter for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Mirjam I LutzInstitute of Neurology, Medical University of Vienna, Vienna, Austria.
Qinwen MaoNeuropathology, Banner Sun Health Research Institute, Sun City, Arizona, USA.
Eliezer MasliahDepartments of Neurosciences and Pathology, University of California, San Diego, La Jolla, California, USA.
Ann C McKeeDepartment of Pathology, VA Medical Center & Boston University School of Medicine, Boston, Massachusetts, USA.
Corey T McMillanDepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
M Marsel MesulamDepartment of Pathology, Northwestern Cognitive Neurology and Alzheimer Disease Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Melissa MurrayDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Peter T NelsonDepartment of Pathology and Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA.
Richard PerrinDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
Thao PhamDepartment of Pathology, Oregon Health Sciences University, Portland, Oregon, USA.
Wayne PoonInstitute for Memory Impairments and Neurological Disorders, UC Irvine, Irvine, California, USA.
Dushyant P PurohitDepartment of Pathology and Nash Family Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Robert A RissmanDepartments of Neurosciences and Pathology, University of California, San Diego, La Jolla, California, USA.
Kenji SakaiDepartment of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Mary SanoDepartment of Psychiatry and Alzheimer's Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Julie A SchneiderDepartments of Pathology and Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.
Thor D SteinDepartment of Pathology, VA Medical Center & Boston University School of Medicine, Boston, Massachusetts, USA.
Andrew F TeichDepartment of Pathology & Cell Biology and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, USA.
John Q TrojanowskiCenter for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Juan C TroncosoDivision of Neuropathology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Jean-Paul VonsattelDepartment of Pathology & Cell Biology and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, USA.
Sandra WeintraubDepartment of Pathology, Northwestern Cognitive Neurology and Alzheimer Disease Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
David A WolkDepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Randall L WoltjerDepartment of Pathology, Oregon Health Sciences University, Portland, Oregon, USA.
Masahito YamadaDepartment of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Lei YuDepartments of Pathology and Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.
Charles L WhiteDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
John F CraryDepartment of Pathology and Nash Family Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Icahn School of Medicine at Mount Sinai · USNorthwestern University · USUniversity of Pennsylvania · USAllen Institute for Brain Science · USColumbia University Irving Medical Center · USThe University of Texas Southwestern Medical Center · USUniversity of California, Irvine · USUniversity of California, San Diego · USWashington University in St. Louis · USBanner Sun Health Research Institute · USBoston University · USEmory University · USKanazawa University · JPMayo Clinic in Florida · USOregon Health & Science University · USRush University Medical Center · USThe University of Texas Health Science Center at San Antonio · USBoston Medical Center · USJohns Hopkins Medicine · USKrembil Brain Institute
Funding
Smartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI Tammie Lee Smith Benzinger · 1985 to 2026
$69.5MTHERAPEUTIC EFFECTS OF INTRA-NASAL INSULIN DETEMIRP50AG005136 · NIA · UNIVERSITY OF WASHINGTON · PI JAYADEY, SUMAN · 1985 to 2019
$57.2MVIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BREWER, JAMES B · 1985 to 2018
$55.4MWASHINGTON UNIVERSITY ALZHEIMERS DISEASE RESEARCH CENTERP50AG005681 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 1985 to 2019
$52.1MThe natural history of AB accumulation in preclinical ADP01AG026276 · NIA · WASHINGTON UNIVERSITY · PI SCHINDLER, SUZANNE ELIZABETH · 2005 to 2025
$49.5MSUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1MSatellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
$46.3MTREATMENT OF DEPRESSION IN ALZHEIMER'S DISEASEP50AG005133 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BECKER, JAMES T. · 1985 to 2019
$43.0MFurthering scientific understanding of mechanisms underlying resilience to the effects of AD pathology by incorporating state of the art quantification of gliosis, inflammation, & synaptic toxicityU01AG006781 · NIA · UNIVERSITY OF WASHINGTON · PI CRANE, PAUL K, LARSON, ERIC B · 1986 to 2020
$39.3MVESICULAR LOCALIZATION AND FUNCTION OF PRESENILIN 1 FRAGMENTP50AG005138 · NIA · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI SCHIMMING, CORBETT · 1985 to 2019
$37.9MTransgenic Mouse Models of Tau PathologiesP01AG017586 · NIA · UNIVERSITY OF PENNSYLVANIA · PI LEE, VIRGINIA M · 2000 to 2021
$37.3MUC Irvine Alzheimer's Disease Research Center Induced Pluripotent Stem Cell CoreP50AG016573 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAFERLA, FRANK M · 2000 to 2019
$37.0MMedical Research Council G0400074NIA NIH HHS F32 AG056098NIA NIH HHS K08 AG065463NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG017586NIA NIH HHS P01 AG026276NIA NIH HHS P30 AG008017NIA NIH HHS P30 AG010124NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG013854NIA NIH HHS P30 AG019610NIA NIH HHS P30 AG028383NIA NIH HHS P30 AG062429NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066507NIA NIH HHS P30 AG066509NIA NIH HHS P30 AG066511NIA NIH HHS P30 AG066514NIA NIH HHS P30 AG066518NIA NIH HHS P30 AG072946NIA NIH HHS P30 AG072979NIA NIH HHS P50 AG005131NIA NIH HHS P50 AG005133NIA NIH HHS P50 AG005136NIA NIH HHS P50 AG005138NIA NIH HHS P50 AG005681NIA NIH HHS P50 AG008702NIA NIH HHS P50 AG016573NIA NIH HHS P50 AG025688NIA NIH HHS R01 AG021055NIA NIH HHS R01 AG054008NIA NIH HHS R01 AG062348NIA NIH HHS R56 AG058732NIA NIH HHS RF1 AG057902NIA NIH HHS U01 AG006781NINDS NIH HHS P30 NS055077NINDS NIH HHS R01 NS095252NINDS NIH HHS RF1 NS095252
Abstract
Primary age-related tauopathy (PART) is a neurodegenerative entity defined as Alzheimer-type neurofibrillary degeneration primarily affecting the medial temporal lobe with minimal to absent amyloid-β (Aβ) plaque deposition. The extent to which PART can be differentiated pathoanatomically from Alzheimer disease (AD) is unclear. Here, we examined the regional distribution of tau pathology in a large cohort of postmortem brains (n = 914). We found an early vulnerability of the CA2 subregion of the hippocampus to neurofibrillary degeneration in PART, and semiquantitative assessment of neurofibrillary degeneration in CA2 was significantly greater than in CA1 in PART. In contrast, subjects harboring intermediate-to-high AD neuropathologic change (ADNC) displayed relative sparing of CA2 until later stages of their disease course. In addition, the CA2/CA1 ratio of neurofibrillary degeneration in PART was significantly higher than in subjects with intermediate-to-high ADNC burden. Furthermore, the distribution of tau pathology in PART diverges from the Braak NFT staging system and Braak stage does not correlate with cognitive function in PART as it does in individuals with intermediate-to-high ADNC. These findings highlight the need for a better understanding of the contribution of PART to cognitive impairment and how neurofibrillary degeneration interacts with Aβ pathology in AD and PART.
Indexed as
AgedAged, 80 and overAgingAmyloid beta-PeptidesCA2 Region, HippocampalFemaleHumansMaleMiddle AgedNeurofibrillary TanglesNeuronsPlaque, AmyloidTauopathiestau ProteinsAmyloid beta-Peptidestau ProteinsAlzheimer diseaseCA2Cognitive statusCornu ammonisHippocampal subfieldsNeurodegenerative diseasePrimary age-related tauopathy
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