Alzheimer Disease Pathogenesis: Insights From Molecular and Cellular Biology Studies of Oligomeric Aβ and Tau Species DOI Creative Commons
Xu‐Qiao Chen, William C. Mobley

Frontiers in Neuroscience, Journal Year: 2019, Volume and Issue: 13

Published: June 21, 2019

Alzheimer disease (AD) represents an oncoming epidemic that without effective treatment promises to exact extraordinary human and financial burdens. Studies of pathogenesis are essential for defining targets discovering disease-modifying treatments. Past studies AD neuropathology provided valuable, albeit limited, insights. Nevertheless, building on these findings, recent have increasingly rich harvest genetic, molecular cellular data creating unprecedented opportunities both understand treat AD. Among the most significant those documenting presence within brain toxic oligomeric species Aβ tau. Existing support view such can propagate spread neural circuits. To place findings in context we first review genetics AD, including Down syndrome. We detail existence while noting unanswered questions concerning their precise structures, means by which they undergo amplification how induce neuronal dysfunction degeneration. conclude offering a speculative synthesis oligomers tau initiate drive pathogenesis. While 100 years after Alzheimer's report there is much still learn about discovery treatments, application new concepts sophisticated tools poised deliver important advances combatting

Language: Английский

Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing DOI
Brian W. Kunkle, Benjamin Grenier‐Boley, Rebecca Sims

et al.

Nature Genetics, Journal Year: 2019, Volume and Issue: 51(3), P. 414 - 430

Published: Feb. 28, 2019

Language: Английский

Citations

2492
Alzheimer Disease: An Update on Pathobiology and Treatment Strategies DOI Creative Commons
Justin M. Long, David M. Holtzman

Cell, Journal Year: 2019, Volume and Issue: 179(2), P. 312 - 339

Published: Sept. 26, 2019

Language: Английский

Citations

2382
Immune attack: the role of inflammation in Alzheimer disease DOI
Frank L. Heppner,

Richard M. Ransohoff,

Burkhard Becher

et al.

Nature reviews. Neuroscience, Journal Year: 2015, Volume and Issue: 16(6), P. 358 - 372

Published: May 20, 2015

Language: Английский

Citations

1900
Alzheimer disease DOI
David S. Knopman, Hélène Amieva, Ronald C. Petersen

et al.

Nature Reviews Disease Primers, Journal Year: 2021, Volume and Issue: 7(1)

Published: May 13, 2021

Language: Английский

Citations

1533
New insights into the genetic etiology of Alzheimer’s disease and related dementias DOI Creative Commons
Céline Bellenguez, Fahri Küçükali, Iris E. Jansen

et al.

Nature Genetics, Journal Year: 2022, Volume and Issue: 54(4), P. 412 - 436

Published: April 1, 2022

Abstract Characterization of the genetic landscape Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for better understanding associated pathophysiological processes. We performed two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases 677,663 controls. found 75 risk loci, which 42 were new at time analysis. Pathway enrichment analyses confirmed involvement amyloid/tau pathways highlighted microglia implication. Gene prioritization in loci identified 31 genes that suggestive genetically processes, including tumor necrosis factor alpha pathway through linear ubiquitin chain assembly complex. also built score with future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement prediction led 1.6- 1.9-fold increase lowest highest decile, addition effects age APOE ε4 allele.

Language: Английский

Citations

1519
New Technologies for Analysis of Extracellular Vesicles DOI
Huilin Shao, Hyungsoon Im, Cesar M. Castro

et al.

Chemical Reviews, Journal Year: 2018, Volume and Issue: 118(4), P. 1917 - 1950

Published: Jan. 31, 2018

Extracellular vesicles (EVs) are diverse, nanoscale membrane actively released by cells. Similar-sized can be further classified (e.g., exosomes, microvesicles) based on their biogenesis, size, and biophysical properties. Although initially thought to cellular debris, thus under-appreciated, EVs now increasingly recognized as important vehicles of intercellular communication circulating biomarkers for disease diagnoses prognosis. Despite clinical potential, the lack sensitive preparatory analytical technologies poses a barrier translation. New platforms including molecular ones being developed address these challenges. Recent advances in field expected have far-reaching impact both basic translational studies. This article aims present comprehensive critical overview emerging EV detection applications.

Language: Английский

Citations

1375
Neurotoxicity of Amyloid -Protein: Synaptic and Network Dysfunction DOI Open Access
Lennart Mucke, Dennis J. Selkoe

Cold Spring Harbor Perspectives in Medicine, Journal Year: 2012, Volume and Issue: 2(7), P. a006338 - a006338

Published: March 13, 2012

Lennart Mucke1 and Dennis J. Selkoe2 Gladstone Institute of Neurological Disease University California, San Francisco, California 94102 Center for Neurologic Diseases, Harvard Medical School Brigham Women's Hospital, Boston, Massachusetts 02115 Correspondence: lmucke{at}gladstone.ucsf.edu, dselkoe{at}rics.bwh.harvard.edu

Language: Английский

Citations

933
TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia DOI Creative Commons
Felix L. Yeh,

Yuanyuan Wang,

Irene Tom

et al.

Neuron, Journal Year: 2016, Volume and Issue: 91(2), P. 328 - 340

Published: July 1, 2016

Language: Английский

Citations

773
Apolipoprotein E and Apolipoprotein E Receptors: Normal Biology and Roles in Alzheimer Disease DOI Open Access
David M. Holtzman,

Joachim Herz,

Guojun Bu

et al.

Cold Spring Harbor Perspectives in Medicine, Journal Year: 2012, Volume and Issue: 2(3), P. a006312 - a006312

Published: Jan. 10, 2012

Apolipoprotein E (APOE) genotype is the major genetic risk factor for Alzheimer disease (AD); ε4 allele increases and ε2 protective. In central nervous system (CNS), apoE produced by glial cells, present in high-density-like lipoproteins, interacts with several receptors that are members of low-density lipoprotein receptor (LDLR) family, a protein binds to amyloid-β (Aβ) peptide. There variety mechanisms which isoform may influence AD. substantial evidence differential effects on AD influenced ability affect Aβ aggregation clearance brain. Other also likely play role CNS function as well AD, including synaptic plasticity, cell signaling, lipid transport metabolism, neuroinflammation. ApoE receptors, LDLRs, Apoer2, very (VLDLRs), receptor-related 1 (LRP1) appear both metabolism toxicity. Therapeutic strategies based include influencing apoE/Aβ interactions, structure, lipidation, LDLR family member function, signaling. Understanding normal disease-related biology connecting apoE, provide novel insights into pathogenesis treatment.

Language: Английский

Citations

740
Disruption of the Sleep-Wake Cycle and Diurnal Fluctuation of β-Amyloid in Mice with Alzheimer’s Disease Pathology DOI
Jee Hoon Roh,

Yafei Huang,

Adam W. Bero

et al.

Science Translational Medicine, Journal Year: 2012, Volume and Issue: 4(150)

Published: Sept. 5, 2012

Decreased sleep and attenuation of circadian fluctuations in Aβ reflect amyloid-associated pathology Alzheimer’s disease.

Language: Английский

Citations

523