Evidence map›Paper›PMID 25092575›Full record

ArticleNeurobiology of disease2014

Intracellular amyloid and the neuronal origin of Alzheimer neuritic plaques.

Anna Pensalfini, Ricardo Albay, Suhail Rasool, Jessica W Wu, Asa Hatami, Hiromi Arai, Lawrence Margol, Saskia Milton, Wayne W Poon, Maria M Corrada and 2 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurobiology of disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
3.1field-weighted citation impact, top 8% of its field
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

72 citing papers in PubMed, 126 citations in OpenAlex.

  1. Article
  2. A lifespan staging model of basal forebrain cholinergic vulnerability.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
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12 more citing papers are in PubMed but not listed here.

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

12 authors at 2 institutions in 2 countries.

Anna PensalfiniDepartment of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA. Electronic address: apensalfini@NKI.RFMH.ORG.
Ricardo AlbayDepartment of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.
Suhail RasoolDepartment of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.
Jessica W WuDepartment of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.
Asa HatamiDepartment of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.
Hiromi AraiDepartment of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.
Lawrence MargolDepartment of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.
Saskia MiltonDepartment of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.
Wayne W PoonInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697, USA.
Maria M CorradaInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697, USA; Department of Neurology, University of California, Irvine, CA 92697, USA.
Claudia H KawasInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697, USA; Department of Neurology, University of California, Irvine, CA 92697, USA; Department of Neurobiology & Behavior, University of California, Irvine, CA 92697, USA.
Charles G GlabeDepartment of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA; Biochemistry Department and Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
University of California, Irvine · USKing Abdulaziz University · SA

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Christine Hui · 1994 to 2026
$57.9M
UC Irvine Alzheimer's Disease Research Center Induced Pluripotent Stem Cell CoreP50AG016573 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAFERLA, FRANK M · 2000 to 2019
$37.0M
Diversity Supplement to R01AG021055; Clinical, Imaging, and Pathological Studies in the Oldest Old: The 90+ StudyR01AG021055 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI CORRADA, MARIA, KAWAS, CLAUDIA H. · 2002 to 2024
$36.9M
TISSUE REPOSITORY COREP01AG000538 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAFERLA, FRANK M · 1985 to 2018
$24.8M
Structure and conformational diversity of amyloid oligomersR01AG033069 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI GLABE, CHARLES G. · 2010 to 2014
$1.4M
Novel nuclear and intracellular pathology in early ADR21AG045729 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI GERSHON, PAUL D, GLABE, CHARLES G. · 2014 to 2015
$431k
NCI NIH HHS P30 CA062203NCI NIH HHS P30CA062203NIA NIH HHS AG00538NIA NIH HHS AG 033069NIA NIH HHS P01 AG000538NIA NIH HHS P50 AG016573NIA NIH HHS P50AG16573NIA NIH HHS R01 AG021055NIA NIH HHS R01 AG033069NIA NIH HHS R01AG21055NIA NIH HHS R21 AG045729
6 · The paper itself

Abstract

Genetic analysis of familial forms of Alzheimer's disease (AD) causally links the proteolytic processing of the amyloid precursor protein (APP) and AD. However, the specific type of amyloid and mechanisms of amyloid pathogenesis remain unclear. We conducted a detailed analysis of intracellular amyloid with an aggregation specific conformation dependent monoclonal antibody, M78, raised against fibrillar Aß42. M78 immunoreactivity colocalizes with Aß and the carboxyl terminus of APP (APP-CTF) immunoreactivities in perinuclear compartments at intermediate times in 10month 3XTg-AD mice, indicating that this represents misfolded and aggregated protein rather than normally folded APP. At 12months, M78 immunoreactivity also accumulates in the nucleus. Neuritic plaques at 12months display the same spatial organization of centrally colocalized M78, diffuse chromatin and neuronal nuclear NeuN staining surrounded by peripheral M78 and APP-CTF immunoreactivity as observed in neurons, indicating that neuritic plaques arise from degenerating neurons with intracellular amyloid immunoreactivity. The same staining pattern was observed in neuritic plaques in human AD brains, showing elevated intracellular M78 immunoreactivity at intermediate stages of amyloid pathology (Braak A and B) compared to no amyloid pathology and late stage amyloid pathology (Braak 0 and C, respectively). These results indicate that intraneuronal protein aggregation and amyloid accumulation is an early event in AD and that neuritic plaques are initiated by the degeneration and death of neurons by a mechanism that may be related to the formation of extracellular traps by neutrophils.

Indexed as

AgedAged, 80 and overAge Factorsalpha-SynucleinAlzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsBrainCell NucleolusCytoplasmDisease Models, AnimalFemaleHumansMaleMicealpha-SynucleinAmyloid beta-Peptidesamyloid beta-protein (1-42)Amyloid beta-Protein PrecursorPeptide FragmentsPhosphopyruvate HydratasePresenilin-1PSEN1 protein, humanAlzheimerIntracellular amyloidNeuritic plaquesNuclear pathology

Identifiers

PMID25092575
PMCPMC4179983
OpenAlexW2005765994

What OpenQuestion holds

Textmetadata
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Read underepoch 390

Registered trials

None linked

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.