Microglia express ABI3 in the brains of Alzheimer's disease and Nasu-Hakola disease

Satoh, Jun‐ichi; Kino, Yoshihiro; Yanaizu, Motoaki; Tosaki, Youhei; Sakai, Kenji; Ishida, Tsuyoshi; Saito, Yuko

doi:10.5582/irdr.2017.01073

Cited by 36 publications

(21 citation statements)

References 29 publications

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“…Mediates phagocytic, involved in microglial Aβ clearance (Aikawa et al, 2018) rs616338 ABI3 Microglial function, actin polymerization (Satoh et al, 2017) rs35349669 INPP5D Microglia function and survival (Efthymiou and Goate, 2017) Lysosomes rs597668 BLOC1S3 Lysosome biogenesis (Zhang et al, 2014) rs8093731 DSG2 Lysosomal function (Karch and Goate, 2015) rs5848 GRN Lysosomal function (Paushter et al, 2018) Astrocytes and lipid metabolism rs5167 APOC4 Lipid metabolism (Riedel et al, 2016) rs2075650 APOE Lipid metabolism, immunomodulation, interacts with TREM2 (Shi and Holtzman, 2018) Immune cell movement and migration rs11767557, rs11771145…”

Section: Abca7mentioning

confidence: 99%

Friend, Foe or Both? Immune Activity in Alzheimer’s Disease

Frost

Jonas

2019

Front. Aging Neurosci.

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Alzheimer's disease (AD) is marked by the presence of amyloid beta (Aβ) plaques, neurofibrillary tangles (NFT), neuronal death and synaptic loss, and inflammation in the brain. AD research has, in large part, been dedicated to the understanding of Aβ and NFT deposition as well as to the pharmacological reduction of these hallmarks. However, recent GWAS data indicates neuroinflammation plays a critical role in AD development, thereby redirecting research efforts toward unveiling the complexities of AD-associated neuroinflammation. It is clear that the innate immune system is intimately associated with AD progression, however, the specific roles of glia and neuroinflammation in AD pathology remain to be described. Moreover, inflammatory processes have largely been painted as detrimental to AD pathology, when in fact, many immune mechanisms such as phagocytosis aid in the reduction of AD pathologies. In this review, we aim to outline the delicate balance between the beneficial and detrimental aspects of immune activation in AD as a more thorough understanding of these processes is critical to development of effective therapeutics for AD.

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Section: Abca7mentioning

confidence: 99%

Friend, Foe or Both? Immune Activity in Alzheimer’s Disease

Frost

Jonas

2019

Front. Aging Neurosci.

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“…In addition, environmental factors that comprise psychosocial stress confer a high risk of developing neurodegenerative diseases and may play an important role in the etiology of sporadic AD ( Alkadhi, 2012 ; Aznar and Knudsen, 2011 ; Nation et al, 2011 ). Genetic risk factors for sporadic AD also include mutations or polymorphisms in several genes expressed by microglia and other myeloid cells ( Dos Santos et al, 2017 ; Efthymiou and Goate, 2017 ; Jonsson et al, 2013 ; Malik et al, 2015 ; Satoh et al, 2017 ; Sims et al, 2017 ), stressing the importance of these immune cells. While the brain is home to perivascular macrophages, as well as monocytes derived from the bone marrow that enter the CNS from the circulation, especially during brain injury or systemic inflammation ( Guillemin and Brew, 2004 ; Schwartz et al, 2013 ; Wohleb et al, 2015 ), microglia are the predominant immune cell population within the CNS.…”

Section: Introduction: Microglia and Alzheimer's Diseasementioning

confidence: 99%

Chronic stress as a risk factor for Alzheimer's disease: Roles of microglia-mediated synaptic remodeling, inflammation, and oxidative stress

Bisht

Sharma

Tremblay

2018

Neurobiology of Stress

290

155

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Microglia are the predominant immune cells of the central nervous system (CNS) that exert key physiological roles required for maintaining CNS homeostasis, notably in response to chronic stress, as well as mediating synaptic plasticity, learning and memory. The repeated exposure to stress confers a higher risk of developing neurodegenerative diseases including sporadic Alzheimer's disease (AD). While microglia have been causally linked to amyloid beta (Aβ) accumulation, tau pathology, neurodegeneration, and synaptic loss in AD, they were also attributed beneficial roles, notably in the phagocytic elimination of Aβ. In this review, we discuss the interactions between chronic stress and AD pathology, overview the roles played by microglia in AD, especially focusing on chronic stress as an environmental risk factor modulating their function, and present recently-described microglial phenotypes associated with neuroprotection in AD. These microglial phenotypes observed under both chronic stress and AD pathology may provide novel opportunities for the development of better-targeted therapeutic interventions.

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“…WRC activates the actin nucleator actin-related protein-2/3 (Arp2/3) to induce actin polymerization, which is necessary for cell motility in many functions including immune responses [ 3 ]. These findings and the identification of ABI3 expressing microglia clusters exclusively in AD brains and around amyloid beta (Aβ) plaques [ 4 ] may suggest a role for ABI3 in microglia motility.…”

Section: Introductionmentioning

confidence: 99%

ABI3 and PLCG2 missense variants as risk factors for neurodegenerative diseases in Caucasians and African Americans

Conway

Carrasquillo

Wang

et al. 2018

Mol Neurodegeneration

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BackgroundRare coding variants ABI3_rs616338-T and PLCG2_rs72824905-G were identified as risk or protective factors, respectively, for Alzheimer’s disease (AD).MethodsWe tested the association of these variants with five neurodegenerative diseases in Caucasian case-control cohorts: 2742 AD, 231 progressive supranuclear palsy (PSP), 838 Parkinson’s disease (PD), 306 dementia with Lewy bodies (DLB) and 150 multiple system atrophy (MSA) vs. 3351 controls; and in an African-American AD case-control cohort (181 AD, 331 controls). 1479 AD and 1491 controls were non-overlapping with a prior report.ResultsUsing Fisher’s exact test, there was significant association of both ABI3_rs616338-T (OR = 1.41, p = 0.044) and PLCG2_rs72824905-G (OR = 0.56, p = 0.008) with AD. These OR estimates were maintained in the non-overlapping replication AD-control analysis, albeit at reduced significance (ABI3_rs616338-T OR = 1.44, p = 0.12; PLCG2_rs72824905-G OR = 0.66, p = 0.19). None of the other cohorts showed significant associations that were concordant with those for AD, although the DLB cohort had suggestive findings (Fisher’s test: ABI3_rs616338-T OR = 1.79, p = 0.097; PLCG2_rs72824905-G OR = 0.32, p = 0.124). PLCG2_rs72824905-G showed suggestive association with pathologically-confirmed MSA (OR = 2.39, p = 0.050) and PSP (OR = 1.97, p = 0.061), although in the opposite direction of that for AD. We assessed RNA sequencing data from 238 temporal cortex (TCX) and 224 cerebellum (CER) samples from AD, PSP and control patients and identified co-expression networks, enriched in microglial genes and immune response GO terms, and which harbor PLCG2 and/or ABI3. These networks had higher expression in AD, but not in PSP TCX, compared to controls. This expression association did not survive adjustment for brain cell type population changes.ConclusionsWe validated the associations previously reported with ABI3_rs616338-T and PLCG2_rs72824905-G in a Caucasian AD case-control cohort, and observed a similar direction of effect in DLB. Conversely, PLCG2_rs72824905-G showed suggestive associations with PSP and MSA in the opposite direction. We identified microglial gene-enriched co-expression networks with significantly higher levels in AD TCX, but not in PSP, a primary tauopathy. This co-expression network association appears to be driven by microglial cell population changes in a brain region affected by AD pathology. Although these findings require replication in larger cohorts, they suggest distinct effects of the microglial genes, ABI3 and PLCG2 in neurodegenerative diseases that harbor significant vs. low/no amyloid ß pathology.Electronic supplementary materialThe online version of this article (10.1186/s13024-018-0289-x) contains supplementary material, which is available to authorized users.

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Microglia express ABI3 in the brains of Alzheimer's disease and Nasu-Hakola disease

Cited by 36 publications

References 29 publications

Friend, Foe or Both? Immune Activity in Alzheimer’s Disease

Friend, Foe or Both? Immune Activity in Alzheimer’s Disease

Chronic stress as a risk factor for Alzheimer's disease: Roles of microglia-mediated synaptic remodeling, inflammation, and oxidative stress

ABI3 and PLCG2 missense variants as risk factors for neurodegenerative diseases in Caucasians and African Americans

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