The Role of APOE and TREM2 in Alzheimer′s Disease—Current Understanding and Perspectives

Untangling Genetic Risk for Alzheimer’s Disease

(2018) Anna A. Pimenova et al.   BIOLOGICAL PSYCHIATRY

APOE genotype and cognition in healthy individuals at risk of Alzheimer's disease: A review

(2018) M. Clare O'Donoghue et al.   CORTEX

Presynaptic endocytic factors in autophagy and neurodegeneration

(2018) Domenico Azarnia Tehran et al.   CURRENT OPINION IN NEUROBIOLOGY

Targeting of nonlipidated, aggregated apoE with antibodies inhibits amyloid accumulation

(2018) Fan Liao et al.   JOURNAL OF CLINICAL INVESTIGATION

ApoE facilitates the microglial response to amyloid plaque pathology

(2018) Jason D. Ulrich et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Humanized TREM2 mice reveal microglia-intrinsic and -extrinsic effects of R47H polymorphism

(2018) Wilbur M. Song et al.   JOURNAL OF EXPERIMENTAL MEDICINE

The Trem2 R47H variant confers loss-of-function-like phenotypes in Alzheimer’s disease

(2018) Paul J. Cheng-Hathaway et al.   Molecular Neurodegeneration

Loss of Trem2 in microglia leads to widespread disruption of cell coexpression networks in mouse brain

(2018) Guillermo Carbajosa et al.   NEUROBIOLOGY OF AGING

TREM2 Is a Receptor for β-Amyloid that Mediates Microglial Function

(2018) Yingjun Zhao et al.   NEURON

Elevated TREM2 Gene Dosage Reprograms Microglia Responsivity and Ameliorates Pathological Phenotypes in Alzheimer’s Disease Models

(2018) C.Y. Daniel Lee et al.   NEURON

Microglial signatures and their role in health and disease

(2018) Oleg Butovsky et al.   NATURE REVIEWS NEUROSCIENCE

Is APOE ε4 required for Alzheimer's disease to develop in TREM2 p.R47H variant carriers?

(2018) Rita Guerreiro et al.   NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY

Soluble TREM2 changes during the clinical course of Alzheimer’s disease: A meta-analysis

(2018) Dan Liu et al.   NEUROSCIENCE LETTERS

CSF soluble TREM2 as a measure of immune response along the Alzheimer's disease continuum

(2018) Boris-Stephan Rauchmann et al.   NEUROBIOLOGY OF AGING

Amyloid precursor protein and endosomal–lysosomal dysfunction in Alzheimer’s disease: inseparable partners in a multifactorial disease

(2017) Ralph A. Nixon   FASEB JOURNAL

The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases

(2017) Susanne Krasemann et al.   IMMUNITY

Soluble TREM2 induces inflammatory responses and enhances microglial survival

(2017) Li Zhong et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Role of LRP1 in the pathogenesis of Alzheimer’s disease: evidence from clinical and preclinical studies

(2017) Mitsuru Shinohara et al.   JOURNAL OF LIPID RESEARCH

The Alzheimer’s disease risk factors apolipoprotein E and TREM2 are linked in a receptor signaling pathway

(2017) Charlotte Jendresen et al.   Journal of Neuroinflammation

TREM2 Promotes Microglial Survival by Activating Wnt/β-Catenin Pathway

(2017) Honghua Zheng et al.   JOURNAL OF NEUROSCIENCE

Astrocyte dysfunction in Alzheimer disease

(2017) Crystal Acosta et al.   JOURNAL OF NEUROSCIENCE RESEARCH

Triggering Receptor Expressed on Myeloid Cells 2 Deficiency Alters Acute Macrophage Distribution and Improves Recovery after Traumatic Brain Injury

(2017) Maha Saber et al.   JOURNAL OF NEUROTRAUMA

ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy

(2017) Yang Shi et al.   NATURE

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

(2017) Rebecca Sims et al.   NATURE GENETICS

Age-Dependent Effects of apoE Reduction Using Antisense Oligonucleotides in a Model of β-amyloidosis

(2017) Tien-Phat V. Huynh et al.   NEURON

ApoE4 Accelerates Early Seeding of Amyloid Pathology

(2017) Chia-Chen Liu et al.   NEURON

Elucidating the Role of TREM2 in Alzheimer’s Disease

(2017) Jason D. Ulrich et al.   NEURON

The blood brain barrier in Alzheimer’s disease

(2017) A. Chakraborty et al.   VASCULAR PHARMACOLOGY

Alzheimer’s disease prevention: from risk factors to early intervention

(2017) Marta Crous-Bou et al.   Alzheimers Research & Therapy

Alzheimer's Disease: The Role of Microglia in Brain Homeostasis and Proteopathy

(2017) Kevin A. Clayton et al.   Frontiers in Neuroscience

Cerebrospinal fluid soluble TREM2 is higher in Alzheimer disease and associated with mutation status

(2016) Laura Piccio et al.   ACTA NEUROPATHOLOGICA

Lymphatic Clearance of the Brain: Perivascular, Paravascular and Significance for Neurodegenerative Diseases

(2016) Erik N. T. P. Bakker et al.   CELLULAR AND MOLECULAR NEUROBIOLOGY

Apolipoprotein E as a Therapeutic Target in Alzheimer’s Disease: A Review of Basic Research and Clinical Evidence

(2016) Yu Yamazaki et al.   CNS DRUGS

Microglial genes regulating neuroinflammation in the progression of Alzheimer's disease

(2016) Claudio Villegas-Llerena et al.   CURRENT OPINION IN NEUROBIOLOGY

TREM2 deficiency reduces the efficacy of immunotherapeutic amyloid clearance

(2016) Xianyuan Xiang et al.   EMBO Molecular Medicine

sTREM2 cerebrospinal fluid levels are a potential biomarker for microglia activity in early‐stage Alzheimer's disease and associate with neuronal injury markers

(2016) Marc Suárez‐Calvet et al.   EMBO Molecular Medicine

TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques

(2016) Yaming Wang et al.   JOURNAL OF EXPERIMENTAL MEDICINE

The Complex Role of Apolipoprotein E in Alzheimer’s Disease: an Overview and Update

(2016) Laura Mahoney-Sanchez et al.   JOURNAL OF MOLECULAR NEUROSCIENCE

Genetic Restoration of Plasma ApoE Improves Cognition and Partially Restores Synaptic Defects in ApoE-Deficient Mice

(2016) C. Lane-Donovan et al.   JOURNAL OF NEUROSCIENCE

Disease Progression-Dependent Effects of TREM2 Deficiency in a Mouse Model of Alzheimer's Disease

(2016) Taylor R. Jay et al.   JOURNAL OF NEUROSCIENCE

Increased cerebrospinal fluid soluble TREM2 concentration in Alzheimer’s disease

(2016) Amanda Heslegrave et al.   Molecular Neurodegeneration

TREM2 variants: new keys to decipher Alzheimer disease pathogenesis

(2016) Marco Colonna et al.   NATURE REVIEWS NEUROSCIENCE

Opposing roles of the triggering receptor expressed on myeloid cells 2 and triggering receptor expressed on myeloid cells-like transcript 2 in microglia activation

(2016) Honghua Zheng et al.   NEUROBIOLOGY OF AGING

Evaluating pathogenic dementia variants in posterior cortical atrophy

(2016) Minerva M. Carrasquillo et al.   NEUROBIOLOGY OF AGING

TREM2 Haplodeficiency in Mice and Humans Impairs the Microglia Barrier Function Leading to Decreased Amyloid Compaction and Severe Axonal Dystrophy

(2016) Peng Yuan et al.   NEURON

TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia

(2016) Felix L. Yeh et al.   NEURON

Neurodegenerative disease mutations in TREM2 reveal a functional surface and distinct loss-of-function mechanisms

(2016) Daniel L Kober et al.   eLife

The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease

(2015) Christina M. Lill et al.   Alzheimers & Dementia

Opposing effects ofApoe/Apoa1double deletion on amyloid-β pathology and cognitive performance in APP mice

(2015) Nicholas F. Fitz et al.   BRAIN

TREM2 Lipid Sensing Sustains the Microglial Response in an Alzheimer’s Disease Model

(2015) Yaming Wang et al.   CELL

Apolipoprotein E Is a Ligand for Triggering Receptor Expressed on Myeloid Cells 2 (TREM2)

(2015) Yuka Atagi et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The Triggering Receptor Expressed on Myeloid Cells 2 Binds Apolipoprotein E

(2015) Charles C. Bailey et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

TREM2 sustains microglial expansion during aging and response to demyelination

(2015) Pietro Luigi Poliani et al.   JOURNAL OF CLINICAL INVESTIGATION

TREM-2 promotes macrophage survival and lung disease after respiratory viral infection

(2015) Kangyun Wu et al.   JOURNAL OF EXPERIMENTAL MEDICINE

TREM2 deficiency eliminates TREM2+inflammatory macrophages and ameliorates pathology in Alzheimer’s disease mouse models

(2015) Taylor R. Jay et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Bexarotene-Activated Retinoid X Receptors Regulate Neuronal Differentiation and Dendritic Complexity

(2015) A. Mounier et al.   JOURNAL OF NEUROSCIENCE

Assessment of TREM2 rs75932628 association with amyotrophic lateral sclerosis in a Chinese population

(2015) Xueping Chen et al.   JOURNAL OF THE NEUROLOGICAL SCIENCES

TREM2 in CNS homeostasis and neurodegenerative disease

(2015) Meghan M. Painter et al.   Molecular Neurodegeneration

TREM2 is associated with increased risk for Alzheimer’s disease in African Americans

(2015) Sheng Chih Jin et al.   Molecular Neurodegeneration

PLD3 gene variants and Alzheimer's disease

(2015) Basavaraj V. Hooli et al.   NATURE

Variable expression of microglial DAP12 and TREM2 genes in Nasu-Hakola disease

(2015) Atsushi Sasaki et al.   NEUROGENETICS

Assessment of TREM2 rs75932628 association with Parkinson’s disease and multiple system atrophy in a Chinese population

(2015) Yongping Chen et al.   NEUROLOGICAL SCIENCES

Cholesterol metabolism and homeostasis in the brain

(2015) Juan Zhang et al.   Protein & Cell

R47H TREM2 variant increases risk of typical early-onset Alzheimer's disease but not of prion or frontotemporal dementia

(2014) Catherine F. Slattery et al.   Alzheimers & Dementia

Reversal of apoE4-Driven Brain Pathology and Behavioral Deficits by Bexarotene

(2014) A. Boehm-Cagan et al.   JOURNAL OF NEUROSCIENCE

Homozygous TREM2 mutation in a family with atypical frontotemporal dementia

(2014) Isabelle Le Ber et al.   NEUROBIOLOGY OF AGING

Investigation of the role of rare TREM2 variants in frontotemporal dementia subtypes

(2014) Mathias Thelen et al.   NEUROBIOLOGY OF AGING

ATP-binding cassette transporter A1: From metabolism to neurodegeneration

(2014) Radosveta Koldamova et al.   NEUROBIOLOGY OF DISEASE

Nuclear receptors in neurodegenerative diseases

(2014) Rebecca Skerrett et al.   NEUROBIOLOGY OF DISEASE

More than Cholesterol Transporters: Lipoprotein Receptors in CNS Function and Neurodegeneration

(2014) Courtney Lane-Donovan et al.   NEURON

ApoE and Aβ in Alzheimer’s Disease: Accidental Encounters or Partners?

(2014) Takahisa Kanekiyo et al.   NEURON

Alzheimer’s Disease Genetics: From the Bench to the Clinic

(2014) Celeste M. Karch et al.   NEURON

TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis

(2014) G. Kleinberger et al.   Science Translational Medicine

Reduced neuronal signaling in the ageing apolipoprotein-E4 targeted replacement female mice

(2014) Shan-May Yong et al.   Scientific Reports

The low-density lipoprotein receptor-related protein 1 and amyloid-β clearance in Alzheimer’s disease

(2014) Takahisa Kanekiyo et al.   Frontiers in Aging Neuroscience

TREM2Variant p.R47H as a Risk Factor for Sporadic Amyotrophic Lateral Sclerosis

(2014) Janet Cady et al.   JAMA Neurology

Blocking the Interaction between Apolipoprotein E and Aβ Reduces Intraneuronal Accumulation of Aβ and Inhibits Synaptic Degeneration

(2013) Magdalena A. Kuszczyk et al.   AMERICAN JOURNAL OF PATHOLOGY

Sequential Proteolytic Processing of the Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) Protein by Ectodomain Shedding and γ-Secretase-dependent Intramembranous Cleavage

(2013) Patrick Wunderlich et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

TREM2 in neurodegeneration: evidence for association of the p.R47H variant with frontotemporal dementia and Parkinson’s disease

(2013) Sruti Rayaprolu et al.   Molecular Neurodegeneration

Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy

(2013) Chia-Chen Liu et al.   Nature Reviews Neurology

Variants in triggering receptor expressed on myeloid cells 2 are associated with both behavioral variant frontotemporal lobar degeneration and Alzheimer's disease

(2013) Margarita Giraldo et al.   NEUROBIOLOGY OF AGING

Investigating the role of rare heterozygous TREM2 variants in Alzheimer's disease and frontotemporal dementia

(2013) Elise Cuyvers et al.   NEUROBIOLOGY OF AGING

Triggering receptor expressed on myeloid cells 2 variant is rare in late-onset Alzheimer's disease in Han Chinese individuals

(2013) Jin-Tai Yu et al.   NEUROBIOLOGY OF AGING

Missense variant in TREML2 protects against Alzheimer's disease

(2013) Bruno A. Benitez et al.   NEUROBIOLOGY OF AGING

GWAS of Cerebrospinal Fluid Tau Levels Identifies Risk Variants for Alzheimer’s Disease

(2013) Carlos Cruchaga et al.   NEURON

ABCA1 dimer-monomer interconversion during HDL generation revealed by single-molecule imaging

(2013) K. O. Nagata et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Comment on "ApoE-Directed Therapeutics Rapidly Clear  -Amyloid and Reverse Deficits in AD Mouse Models"

(2013) N. F. Fitz et al.   SCIENCE

Comment on "ApoE-Directed Therapeutics Rapidly Clear  -Amyloid and Reverse Deficits in AD Mouse Models"

(2013) I. Tesseur et al.   SCIENCE

Comment on "ApoE-Directed Therapeutics Rapidly Clear  -Amyloid and Reverse Deficits in AD Mouse Models"

(2013) K. Veeraraghavalu et al.   SCIENCE

Comment on "ApoE-Directed Therapeutics Rapidly Clear  -Amyloid and Reverse Deficits in AD Mouse Models"

(2013) A. R. Price et al.   SCIENCE

The Genetics of Alzheimer Disease

(2013) R. E. Tanzi   Cold Spring Harbor Perspectives in Medicine

Using Exome Sequencing to Reveal Mutations in TREM2 Presenting as a Frontotemporal Dementia–like Syndrome Without Bone Involvement

(2013) Rita João Guerreiro et al.   JAMA Neurology

APOE genotype alters glial activation and loss of synaptic markers in mice

(2012) Yuangui Zhu et al.   GLIA

Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Aβ amyloidosis

(2012) Jungsu Kim et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Abca1 Deficiency Affects Alzheimer's Disease-Like Phenotype in Human ApoE4 But Not in ApoE3-Targeted Replacement Mice

(2012) N. F. Fitz et al.   JOURNAL OF NEUROSCIENCE

Mechanisms Underlying the Rapid Peroxisome Proliferator-Activated Receptor- -Mediated Amyloid Clearance and Reversal of Cognitive Deficits in a Murine Model of Alzheimer's Disease

(2012) S. Mandrekar-Colucci et al.   JOURNAL OF NEUROSCIENCE

Variant of TREM2 Associated with the Risk of Alzheimer's Disease

(2012) Thorlakur Jonsson et al.   NEW ENGLAND JOURNAL OF MEDICINE

TREM2 Variants in Alzheimer's Disease

(2012) Rita Guerreiro et al.   NEW ENGLAND JOURNAL OF MEDICINE

ApoE-Directed Therapeutics Rapidly Clear  -Amyloid and Reverse Deficits in AD Mouse Models

(2012) P. E. Cramer et al.   SCIENCE

Synapses and Alzheimer's Disease

(2012) M. Sheng et al.   Cold Spring Harbor Perspectives in Biology

Structure-dependent Impairment of Intracellular Apolipoprotein E4 Trafficking and Its Detrimental Effects Are Rescued by Small-molecule Structure Correctors

(2011) Jens Brodbeck et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Haploinsufficiency of Human APOE Reduces Amyloid Deposition in a Mouse Model of Amyloid-  Amyloidosis

(2011) J. Kim et al.   JOURNAL OF NEUROSCIENCE

Alzheimer's disease: synapses gone cold

(2011) Robert M Koffie et al.   Molecular Neurodegeneration

Alzheimer's Disease: The Challenge of the Second Century

(2011) D. M. Holtzman et al.   Science Translational Medicine

Human apoE Isoforms Differentially Regulate Brain Amyloid-  Peptide Clearance

(2011) J. M. Castellano et al.   Science Translational Medicine

The role of ATP-binding cassette transporter A1 in Alzheimer's disease and neurodegeneration

(2010) Radosveta Koldamova et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS

Nasu-Hakola disease with a splicing mutation of TREM2 in a Japanese family

(2010) Y. Numasawa et al.   EUROPEAN JOURNAL OF NEUROLOGY

Apolipoprotein E4 Domain Interaction Mediates Detrimental Effects on Mitochondria and Is a Potential Therapeutic Target for Alzheimer Disease

(2010) Hung-Kai Chen et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The genetic architecture of Alzheimer's disease: beyond APP, PSENs and APOE

(2010) Rita J. Guerreiro et al.   NEUROBIOLOGY OF AGING

Immunohistochemical characterization of microglia in Nasu-Hakola disease brains

(2010) Jun-ichi Satoh et al.   NEUROPATHOLOGY

ApoE4 reduces glutamate receptor function and synaptic plasticity by selectively impairing ApoE receptor recycling

(2010) Y. Chen et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

TREM2- and DAP12-Dependent Activation of PI3K Requires DAP10 and Is Inhibited by SHIP1

(2010) Q. Peng et al.   Science Signaling

A role for TREM2 ligands in the phagocytosis of apoptotic neuronal cells by microglia

(2009) Christine L. Hsieh et al.   JOURNAL OF NEUROCHEMISTRY

ApoE4 Decreases Spine Density and Dendritic Complexity in Cortical Neurons In Vivo

(2009) S. B. Dumanis et al.   JOURNAL OF NEUROSCIENCE

Human APOE Isoform-Dependent Effects on Brain  -Amyloid Levels in PDAPP Transgenic Mice

(2009) K. R. Bales et al.   JOURNAL OF NEUROSCIENCE

Macrophage colony-stimulating factor induces the proliferation and survival of macrophages via a pathway involving DAP12 and β-catenin

(2009) Karel Otero et al.   NATURE IMMUNOLOGY

Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy

(2009) Guojun Bu   NATURE REVIEWS NEUROSCIENCE

Liver X receptor activation restores memory in aged AD mice without reducing amyloid

(2009) Tim Vanmierlo et al.   NEUROBIOLOGY OF AGING

The effects of apolipoprotein E on non-impaired cognitive functioning: A meta-analysis

(2009) Nick M. Wisdom et al.   NEUROBIOLOGY OF AGING

Apolipoprotein E ε4 is associated with disease-specific effects on brain atrophy in Alzheimer's disease and frontotemporal dementia

(2009) Federica Agosta et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Mutations inTREM2lead to pure early-onset dementia without bone cysts

(2008) Eliane Chouery et al.   HUMAN MUTATION

Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease

(2008) Suzanne E. Wahrle et al.   JOURNAL OF CLINICAL INVESTIGATION

Apolipoprotein E: structure determines function, from atherosclerosis to Alzheimer's disease to AIDS

(2008) Robert W. Mahley et al.   JOURNAL OF LIPID RESEARCH

APOE  4 allele predicts faster cognitive decline in mild Alzheimer disease

(2008) S. Cosentino et al.   NEUROLOGY

ApoE Promotes the Proteolytic Degradation of Aβ

(2008) Qingguang Jiang et al.   NEURON

Mechanisms of microglia accumulation in Alzheimer’s disease: therapeutic implications

(2008) Joseph El Khoury et al.   TRENDS IN PHARMACOLOGICAL SCIENCES