Evidence map›Paper›PMID 31683476›Full record

ArticleJournal of Alzheimer's disease : JAD2019

Abnormalities of DYRK1A-Cytoskeleton Complexes in the Blood Cells as Potential Biomarkers of Alzheimer's Disease.

Karol Dowjat, Tatyana Adayev, Urszula Wojda, Katarzyna Brzozowska, Anna Barczak, Tomasz Gabryelewicz, Yu-Wen Hwang

Open access · bronzeAbstract read
In one paragraph

Article in Journal of Alzheimer's disease : JAD, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.3field-weighted citation impact, top 18% 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

5 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Review
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

7 authors at 3 institutions in 2 countries.

Karol DowjatDepartment of Developmental Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, NY, USA.
Tatyana AdayevDepartment of Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, NY, USA.
Urszula WojdaLaboratory of Preclinical Testing of Higher Standard, Neurobiology Center, Nencki Institute of Experimental Biology, Warsaw, Poland.
Katarzyna BrzozowskaLaboratory of Preclinical Testing of Higher Standard, Neurobiology Center, Nencki Institute of Experimental Biology, Warsaw, Poland.
Anna BarczakDepartment of Neurodegenerative Disorders, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
Tomasz GabryelewiczDepartment of Neurodegenerative Disorders, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
Yu-Wen HwangDepartment of Molecular Biology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, NY, USA.
New York State Office for People With Developmental Disabilities · USInstytut Biologii Doświadczalnej im. Marcelego Nenckiego · PLMossakowski Medical Research Institute, Polish Academy of Sciences · PL

Funding

The role of Mnbk in DS brain development and agingR01HD043960 · NICHD · INSTITUTE FOR BASIC RES IN DEV DISABIL · PI WEGIEL, JERZY · 2004 to 2008
$2.6M
NICHD NIH HHS R01 HD043960
6 · The paper itself

Abstract

backgroundDYRK1A is implicated in mental retardation and Alzheimer's disease (AD) dementia of Down syndrome (DS) individuals. The protein is associated with cytoskeleton and altered expression has been shown to impair the cytoskeletal network via dosage effect.

objectiveOur original observations of marked reduction of cytoskeletal proteins associated with DYRK1A in brains and lymphoblastoid cell lines from DS and AD prompted an investigation whether cytoskeleton abnormalities could potentially be used as biomarkers of AD.

methodsOur assay relied on quantification of co-immunoprecipitated cytoskeletal proteins with DYRK1A (co-IP assay) and analysis of the profile of G- and F-actin fractions obtained by high-speed centrifugations (spin-down assay).

resultsIn co-IP assay, both DS and AD samples displayed reduced abundance of associated cytoskeletal proteins. In spin-down assay, G-actin fractions of controls displayed two closely spaced bands of actin in SDS-PAGE; while in AD and DS, only the upper band of the doublet was present. In both assays, alterations of actin cytoskeleton were present in DS, sporadic and familial AD cases, and in asymptomatic persons who later progressed to confirmed AD, but not in non-AD donors. In blind testing involving six AD and six controls, the above tests positively identified ten cases. Analysis of blood samples revealed the diversity of mild cognitive impairment (MCI) cases regarding the presence of the AD biomarker allowing distinction between likely prodromal AD and non-AD MCI cases.

conclusionsBoth brain tissue and lymphocytes from DS and AD displayed similar semi-quantitative and qualitative alterations of actin cytoskeleton. Their specificity for AD-type dementia and the presence before clinical onset of the disease make them suitable biomarker candidates for early and definite diagnosis of AD. The presence of alterations in peripheral tissue points to systemic underlying mechanisms and suggests that early dysfunction of cytoskeleton may be a predisposing factor in the development of AD.

Indexed as

ActinsAdolescentAdultAgedAged, 80 and overAlzheimer DiseaseBiomarkersCell LineCognitive DysfunctionCytoskeletonDyrk KinasesFemaleHumansImmunoprecipitationLeukocytes, MononuclearMaleActinsBiomarkersDyrk KinasesProtein Serine-Threonine KinasesProtein-Tyrosine KinasesActin cytoskeletonAD biomarkersAlzheimer’s diseasediagnostic tests in blood cellsDown syndromeDYRK1A

Identifiers

PMID31683476
PMCPMC6971831
OpenAlexW2982659443

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.