Evidence map›Paper›PMID 36744338›Full record

ArticleJournal of Alzheimer's disease : JAD2023

Accumulation of pTau231 at the Postsynaptic Density in Early Alzheimer's Disease.

Jaclyn Lilek, Kaouther Ajroud, Alexander Z Feldman, Sesha Krishnamachari, Shadi Ghourchian, Tamar Gefen, Callen L Spencer, Allegra Kawles, Qinwen Mao, Jessica F Tranovich and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of Alzheimer's disease : JAD, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. The Nun Study: Insights from 30 years of aging and dementia research.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Review
  5. Article
  6. Review
  7. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Jaclyn LilekDepartment of Pathology, Northwestern University, Illinois, USA.
Kaouther AjroudDepartment of Pathology, Northwestern University, Illinois, USA.
Alexander Z FeldmanDepartment of Pathology, Northwestern University, Illinois, USA.
Sesha KrishnamachariDepartment of Pathology, University of Minnesota, Minnesota, USA.
Shadi GhourchianDepartment of Pathology, Northwestern University, Illinois, USA.
Tamar GefenMesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University, Illinois, USA.
Callen L SpencerMesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University, Illinois, USA.
Allegra KawlesMesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University, Illinois, USA.
Qinwen MaoDepartment of Pathology, Northwestern University, Illinois, USA.
Jessica F TranovichDepartment of Neuroscience, Mayo Clinic, Florida, USA.
Clifford R JackDepartment of Radiology, Mayo Clinic, Minnesota, USA.
M-Marsel MesulamMesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University, Illinois, USA.
R Ross ReichardDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Minnesota, USA.
Hui ZhangMesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University, Illinois, USA.
Melissa E MurrayDepartment of Neuroscience, Mayo Clinic, Florida, USA.
David KnopmanDepartment of Neurology, Mayo Clinic, Minnesota, USA.
Dennis W DicksonDepartment of Neuroscience, Mayo Clinic, Florida, USA.
Ronald C PetersenDepartment of Neurology, Mayo Clinic, Minnesota, USA.
Benjamin SmithDepartment of Neurology, University of Minnesota, Minnesota, USA.
Karen H AsheDepartment of Neurology, University of Minnesota, Minnesota, USA.
Michelle M MielkeDepartment of Epidemiology and Prevention, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Kathryn M NelsonDepartment of Medicinal Chemistry, Institute for Therapeutics Discovery and Development, University of Minnesota, Minnesota, USA.
Margaret E FlanaganDepartment of Pathology, Northwestern University, Illinois, USA.

Funding

SUPPLEMENT TO ALZHEIMERS DISEASE PATIENT REGISTRYU01AG006786 · NIA · MAYO CLINIC ROCHESTER · PI GRAFF-RADFORD, JONATHAN, JACK, CLIFFORD R. · 1986 to 2023
$49.6M
Research Education ComponentP30AG062677 · NIA · MAYO CLINIC ROCHESTER · PI NILUFER ERTEKIN-TANER · 2019 to 2026
$33.5M
Neuropathology CoreP30AG013854 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI MESULAM, MAREK-MARSEL M · 1996 to 2020
$28.9M
Clinical, Neuroanatomic, and Pathologic Signatures of FTLD-tau in Dementia Phenotypes - Diversity Supplement (Antwan Howard)R01AG062566 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI GEFEN, TAMAR D · 2020 to 2024
$2.1M
nvestigating the role of neuroinflammation in Limbic-predominant age related TDP43 encephalopathyK08AG065463 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI FLANAGAN, MARGARET E · 2020 to 2024
$816k
NIA NIH HHS K08 AG065463NIA NIH HHS P30 AG013854NIA NIH HHS P30 AG062677NIA NIH HHS R01 AG062566NIA NIH HHS U01 AG006786
6 · The paper itself

Abstract

backgroundPhosphorylated cytoplasmic tau inclusions correlate with and precede cognitive deficits in Alzheimer's disease (AD). However, pathological tau accumulation and relationships to synaptic changes remain unclear.

objectiveTo address this, we examined postmortem brain from 50 individuals with the full spectrum of AD (clinically and neuropathologically). Total tau, pTau231, and AMPA GluR1 were compared across two brain regions (entorhinal and middle frontal cortices), as well as clinically stratified groups (control, amnestic mild cognitive impairment, AD dementia), NIA-AA Alzheimer's Disease Neuropathologic Change designations (Not, Low, Intermediate, High), and Braak tangle stages (1-6). Significant co-existing pathology was excluded to isolate changes attributed to pathologic AD.

methodsSynaptosomal fractionation and staining were performed to measure changes in total Tau, pTau231, and AMPA GluR1. Total Tau and pTau231 were quantified in synaptosomal fractions using Quanterix Simoa HD-X.

resultsIncreasing pTau231 in frontal postsynaptic fractions correlated positively with increasing clinical and neuropathological AD severity. Frontal cortex is representative of early AD, as it does not become involved by tau tangles until late in AD. Entorhinal total tau was significantly higher in the amnestic mild cognitive impairment group when compared to AD, but only after accounting for AD associated synaptic changes. Alterations in AMPA GluR1 observed in the entorhinal cortex, but not middle frontal cortex, suggest that pTau231 mislocalization and aggregation in postsynaptic structures may impair glutamatergic signaling by promoting AMPA receptor dephosphorylation and internalization.

conclusionResults highlight the potential effectiveness of early pharmacological interventions targeting pTau231 accumulation at the postsynaptic density.

Indexed as

Alzheimer DiseaseCognitive Dysfunctionalpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic AcidBrainHumansPost-Synaptic Densitytau Proteinsalpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acidtau ProteinsAlzheimer’s diseasecognitive impairmentphosphorylated tauPSD-95Simoa Quanterixsynaptic dysfunctionsynaptophysintau

Identifiers

PMID36744338
PMCPMC10041451

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.