Microglia constitute a barrier that prevents neurotoxic protofibrillar Aβ42 hotspots around plaques
Open accessAbstract
In Alzheimer’s disease (AD), β-amyloid (Aβ) plaques are tightly enveloped by microglia processes, but the significance of this phenomenon is unknown. Here we show that microglia constitute a barrier with profound impact on plaque composition and toxicity. Using high-resolution confocal and in vivo two-photon imaging in AD mouse models, we demonstrate that this barrier prevents outward plaque expansion and leads to compact plaque microregions with low Aβ42 affinity. Areas uncovered by microglia are less compact but have high Aβ42 affinity, leading to the formation of protofibrillar Aβ42 hotspots that are associated with more severe axonal dystrophy. In ageing, microglia coverage is reduced leading to enlarged protofibrillar Aβ42 hotspots and more severe neuritic dystrophy. CX3CR1 gene deletion or anti-Aβ immunotherapy causes expansion of microglia coverage and reduced neuritic dystrophy. Failure of the microglia barrier and the accumulation of neurotoxic protofibrillar Aβ hotspots may constitute novel therapeutic and clinical imaging targets for AD. In Alzheimer’s disease (AD), β-amyloid plaques are tightly enveloped by microglia but the significance of this phenomenon is unknown. Here the authors used confocal and in vivotwo-photon imaging in AD mouse models and revealed that microglia constitute a barrier that seems to prevent the formation of neurotoxic hotspots of protofibrillar β-amyloid.
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Another possibility explaining the protective effect of reduced phagocytic uptake is that microglial cells with PU.1 knock-down may continue to maintain a barrier around amyloid plaques, which insulates toxic Aβ42 and improves cognition in mice independent of phagocytic activity.
“Another possibility explaining the protective effect of a reduction in phagocytic uptake is that microglial cells with PU.1 knock-down may continue to maintain a barrier around the amyloid plaques, which has been shown to insulate toxic Aβ42 and improve cognition in mice independent of microglial phagocytic activity based on studies of Trem2−/−mice (Condello et al., 2015; Yuan et al., 2016).”
From Alzheimer's-associated PU.1 expression levels regulate microglial inflammatory response (2021) · cites this paper as Condello et al., 2015
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredMicroglia form a barrier to prevent Aβ plaques from expanding outward, and areas deficient in microglia exhibit increased Aβ plaque burden and severe axonal degeneration.
“High-resolution confocal and in vivo two-photon imaging have demonstrated that microglia form a barrier to prevent Aβ plaques from expanding outward, with areas deficient in microglia exhibiting increased Aβ plaque burden and severe axonal degeneration (Condello et al. 2015).”
From Changes of the Primary Cilia in Alzheimer's Disease Pathogenesis (2025) · cites this paper as Condello et al. 2015
The Introduction says the imaging showed that microglia restrict the radial expansion of plaques. The Results section on neuritic dystrophy reports greater axonal dystrophy in plaque regions lacking microglial processes, alongside local accumulation of protofibrillar Aβ42. It does not establish increased overall Aβ plaque burden in those areas; local hotspots are narrower than that claim. The indexed passages provide section labels but no page numbers. (LLM, conf=0.86)
Experimental — accuracy not yet measuredEfficient microglial clustering around plaques is essential for Aβ clearance and restricting local Aβ toxicity.
“Because ef fi cient microglial clustering around plaques is essential for A β clearance and restricting local A β toxicity 25,26 , we next assessed plaque-microglia interactions by co-staining Iba1 with X-34.”
From APOE2 attenuates APOE4-associated amyloid pathology and related toxicity in a mouse model of Alzheimer’s disease (2026) · cites this paper as [25]
The Results (Modulation of the microglia barrier ameliorates plaque neurotoxicity; page unavailable) report that greater microglial coverage reduces local toxicity, particularly around small, early-stage plaques. The Introduction says microglia are ineffective at phagocytosing fibrillar plaques, while the Discussion describes clearance-related mechanisms for other Aβ forms as possible contributors. The paper therefore does not establish that clustering is essential for Aβ clearance. (LLM, conf=0.88)
Experimental — accuracy not yet measuredMicroglia form a critical interface between APOE genotype and amyloid pathology, mediating Aβ clearance and restricting local toxicity.
“Microglia form a critical interface between APOE genotype and amyloid pathology, mediating A β clearance and restricting local toxicity 25,40 .”
From APOE2 attenuates APOE4-associated amyloid pathology and related toxicity in a mouse model of Alzheimer’s disease (2026) · cites this paper as [25]
The Introduction describes a proposed role for microglia in Aβ clearance, and the Discussion reports that microglial coverage limits protofibrillar Aβ hotspots and neuritic damage. The paper does not establish an interface between APOE genotype and amyloid pathology, and it presents clearance as a possible mechanism rather than a demonstrated basis for the protective barrier. Page numbers are unavailable in our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measuredMicroglia promote the clearance of Aβ aggregates.
“promotes the clearance of Aβ aggregates.47, 48”
From Acoustofluidic assembly of 3D neurospheroids to model Alzheimer's disease (2020) · cites this paper as [48]
The Introduction says microglia can take up pre-fibrillar Aβ, and the Discussion describes phagocytosis of oligomeric Aβ. But the Introduction also says microglia are very ineffective at phagocytosing fibrillar amyloid deposits, so the unqualified claim about Aβ aggregates is broader than the paper supports. The supplied copy gives section labels but no page numbers. (LLM, conf=0.86)
Experimental — accuracy not yet measured
TREM2 and TAM receptors aid in the compaction of amyloid plaques from a diffuse form, which is more neurotoxic and promotes neurite dystrophy, to a dense-core form associated with lower neurotoxicity.
“TREM2 and TAM receptors were suggested to aid in the compaction of amyloid plaques from a diffuse form, which are more neurotoxic and promote neurite dystrophy, to a dense-core form associated with lower neurotoxicity [153, 162, 163].”
From Microglial function, INPP5D/SHIP1 signaling, and NLRP3 inflammasome activation: implications for Alzheimer’s disease (2023) · cites this paper as [162]
The Discussion (page not provided) says microglial envelopment increases plaque compaction while limiting potentially neurotoxic protofibrillar Aβ, and the Results associate microglia-covered regions with fewer dystrophic neurites. The paper does not establish that TREM2 or TAM receptors drive this process or describe a receptor-mediated transition from diffuse to dense-core plaques; it mentions TREM2 only in connection with Alzheimer’s disease risk. (LLM, conf=0.88)
Experimental — accuracy not yet measuredMicroglia form stable, protective barriers around Aβ plaques and compact Aβ into tightly packed, less toxic forms.
“Microglia are deployed to form stable, protective barriers around Aβ plaques in the AD brain, and work to compact Aβ into tightly packed, less toxic forms (Casali et al., 2020; Condello et al., 2015; Zhao et al., 2017).”
From Alzheimer’s genetic risk factor CASS4 controls microglial focal adhesion biology and amyloidosis (2026) · cites this paper as Condello et al., 2015
The Discussion describes a protective microglial barrier that is relatively stable over months and increases plaque compaction while limiting potentially neurotoxic Aβ hotspots. But the findings were demonstrated in AD mouse models; the Discussion explicitly says that the barrier’s role in human Alzheimer’s disease remains to be determined, so the unqualified reference to the AD brain is broader than the evidence. (LLM, conf=0.85)
Experimental — accuracy not yet measuredMicroglia can use their highly dynamic and mobile processes to compact Aβ fibrils into tightly packed aggregates, reducing Aβ aggregate surface area and limiting their potential neurotoxic effects on nearby neurons.
“They can also use their highly dynamic and mobile processes to compact Aβ fibrils into tightly packed aggregates, reducing Aβ aggregate surface area and thereby limiting their potential neurotoxic effects on nearby neurons (Casali et al., 2020; Condello et al., 2015; Zhao et al., 2017).”
From Alzheimer’s genetic risk factor CASS4 controls microglial focal adhesion biology and amyloidosis (2026) · cites this paper as Condello et al., 2015
The Results section (‘Aβ42 hotspots are anti-colocalized with microglia processes’; page unavailable) links microglial coverage to denser amyloid and less soluble Aβ42 binding, while the Discussion proposes that processes may promote fibril compaction and limit nearby neuritic damage. But the paper does not establish reduced aggregate surface area as the mechanism, and its Results say plaque-contacting processes were highly stable, unlike the motile processes away from plaques. The claim therefore overstates both the proposed mechanism and the role of process mobility. (LLM, conf=0.88)
Experimental — accuracy not yet measuredActivated microglia have been implicated in clearing Aβ through phagocytosis.
“These activated microglia have been implicated in the clearance of Aβ through phagocytosis23,24.”
From Deletion of SPI1 in microglia exacerbates amyloid pathology by impairing microglial response in Alzheimer’s disease models (2026) · cites this paper as [24]
Alzheimer's disease is associated with diverse phenotypic changes in microglia, resulting in distinct microglial states, including protective and harmful states.
“Alzheimer’s disease is associated with diverse phenotypic changes in microglia5,6, resulting in distinct microglial states, including protective (aimed at amyloid clearance and neuroprotection7–9) and harmful (associated with microglia-driven neuroinflammation and toxicity)10,11.”
From Lymphoid gene expression supports neuroprotective microglia function (2025) · cites this paper as [7]
Microglia are critically involved in ensuring the proper containment and removal of neurotoxic material in neurodegenerative disease pathogenesis.
“Mounting evidence suggests that microglia, which are the professional phagocytes of the CNS, are critically involved in ensuring the proper containment and removal of neurotoxic material in neurodegenerative disease pathogenesis (Condello et al., 2015; Hickman et al., 2018; Lampron et al., 2015).”
From SYK coordinates neuroprotective microglial responses in neurodegenerative disease (2022) · cites this paper as Condello et al., 2015
Reactive microglia form a physical barrier believed to restrict plaque propagation.
“form a physical barrier believed to restrict plaque propagation13,14”
From Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer’s disease (2025) · cites this paper as [13]
Microglia accumulation in 3D Aβ+ neurospheroids is consistent with previous findings in human AD brains and mouse models.
“the results were consistent with the previous findings in human AD brains and mouse models,45, 48”
From Acoustofluidic assembly of 3D neurospheroids to model Alzheimer's disease (2020) · cites this paper as [48]
The observed relation of coverage and aggregate size is consistent with a previous in vivo study.
“The observed relation of coverage and aggregate size was consistent with the previous in vivo study,48”
From Acoustofluidic assembly of 3D neurospheroids to model Alzheimer's disease (2020) · cites this paper as [48]
Microglia form a protective barrier to protect brain tissue from the neurotoxicity of Aβ plaques.
“forming a protective barrier to protect brain tissue from the neurotoxicity of Aβ plaques”
From Acoustofluidic assembly of 3D neurospheroids to model Alzheimer's disease (2020) · cites this paper as [48]
In regions lacking microglial processes, neuritic dystrophy is more severe, and these protective mechanisms are reduced during aging.
“Moreover, in regions lacking microglial processes, neuritic dystrophy is more severe, and these protective mechanisms are reduced during aging [15].”
From Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer’s disease (2024) · cites this paper as [15]
Microglial coverage of amyloid plaques serves as a barrier to reduce exposure of neurotoxic protofibrillar Aβ hotspots to neurites.
“Microglial coverage of amyloid plaques also serves as a barrier to reduce exposure of neurotoxic protofibrillar Aβ hotspots to neurites7.”
From Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease (2024) · cites this paper as [7]
Amyloid plaques are typically surrounded by a halo of dystrophic neuronal membranes.
“Amyloid plaques are typically surrounded by a halo of dystrophic neuronal membranes7.”
From Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease (2024) · cites this paper as [7]
Microglia form a protective barrier around Aβ plaques to safeguard the brain from their neurotoxic effects.
“Microglia form a protective barrier around these Aβ plaques to safeguard the brain from their neurotoxic effects (15, 16).”
From Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model (2025) · cites this paper as [16]
The degree of plaque compaction positively correlates with neuronal health.
“These protective functions of microglia have been shown to limit axonal dystrophy to neurons in the immediate area, with the degree of plaque compaction positively correlating with neuronal health (Casali et al., 2020; Condello et al., 2015; Zhao et al., 2017).”
From Alzheimer’s genetic risk factor CASS4 controls microglial focal adhesion biology and amyloidosis (2026) · cites this paper as Condello et al., 2015
Microglia migrate to Aβ pathology and form stable, protective barriers around them.
“Microglia are known to mi grate to Aβ pathology and form stable, protective barriers around them (Condello et al., 2015).”
From Alzheimer’s genetic risk factor CASS4 controls microglial focal adhesion biology and amyloidosis (2026) · cites this paper as Condello et al., 2015
LAMP1 accumulates in dystrophic neurites around plaques.
“Plaque-induced neuritic damage was assessed by staining for lysosomal-associated membrane protein 1 (LAMP1), which accumulates in dystrophic neurites around plaques [50].”
From APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology (2025) · cites this paper as [50]
Microglial Syk is essential for Aβ clearance, and its deficiency exacerbates Aβ pathology in a mouse model.
“Intriguingly, recent studies revealed that microglial Syk is essential for Aβ clearance, with its deficiency exacerbating Aβ pathology in a mouse model24,52.”
From Deletion of SPI1 in microglia exacerbates amyloid pathology by impairing microglial response in Alzheimer’s disease models (2026) · cites this paper as [24]
The Introduction discusses a possible role for microglia in Aβ clearance, and the Results examine CX3CR1 manipulation and plaque neurotoxicity. Searches for Syk and Syk deficiency found no passage in our copy addressing whether microglial Syk is essential for clearance or whether its deficiency exacerbates Aβ pathology. (LLM, conf=0.75)
Experimental — accuracy not yet measuredThe absence of ramified microglial cells may stem from BV-2 cells being a transformed microglia cell line with different morphology compared to microglia directly isolated from animals.
“This may stem from the BV-2 cells, a transformed microglia cell line with differed morphology compared to microglia directly isolated from the animals,48 which was reported previously.51–53”
From Acoustofluidic assembly of 3D neurospheroids to model Alzheimer's disease (2020) · cites this paper as [48]
The Introduction describes plaque-associated microglial morphology, and the Methods describe imaging microglia in mice. Neither addresses BV-2 cells, whether their morphology differs from microglia isolated from animals, or whether that difference explains an absence of ramified cells. Searches for BV-2 and the proposed morphology comparison found no supporting passage in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measuredProtective corralling functions were more readily observed for small, early stage plaques and appeared compromised in mice lacking one or both copies of Trem2, as well as in human AD tissues from TREM2 R47H carriers.
“These protective “corralling” functions were more readily observed for small, early stage plaques and appeared compromised in mice lacking one or both copies of Trem2, as well as in human AD tissues from TREM2 R47H carriers (Condello et al., 2015; Wang et al., 2016; Yuan et al., 2016).”
From Microglia in Alzheimer’s disease (2018) · cites this paper as Condello et al., 2015
Microglia form a protective barrier around amyloid deposits, compacting amyloid fibrils into a tightly packed and potentially less toxic form, preventing the accretion of new Aβ onto existing plaques, and reducing axonal dystrophy in the nearby neuropil.
“Recent evidence suggests that microglia form a protective barrier around amyloid deposits, compacting amyloid fibrils into a tightly packed and potentially less toxic form, preventing the accretion of new Aβ onto existing plaques, and reducing axonal dystrophy in the nearby neuropil (Condello et al., 2015).”
From Microglia in Alzheimer’s disease (2018) · cites this paper as Condello et al., 2015
With β-amyloid deposition, some microglial processes become static, showing stable association with plaques over days or weeks, with TREM2, DAP12, and phosphotyrosine concentrated in processes adjacent to plaques.
“With β-amyloid deposition, however, some microglial processes become static, showing stable association with plaques over days or weeks, with TREM2, DAP12, and phosphotyrosine concentrated in those processes adjacent to plaques (Condello et al., 2015; Yuan et al., 2016).”
From Microglia in Alzheimer’s disease (2018) · cites this paper as Condello et al., 2015
Prior studies show that microglia form a physical barrier around plaques and compact Aβ into dense deposits, protecting against local neurite damage.
“These results are consistent with prior studies showing that microglia form a physical barrier around plaques and compact Aβ into dense deposits, protecting against local neurite damage35–37.”
From Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer’s disease model (2019) · cites this paper as [35]
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Crowded Cell-like Environment Accelerates the Nucleation Step of Amyloidogenic Protein Misfolding
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Curcuminoid Binds to Amyloid-β1-42 Oligomer and Fibril
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High Pressure Promotes Circularly Shaped Insulin Amyloid
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- [47]Mandrekar S Microglia mediate the clearance of soluble Abeta through fluid phase macropinocytosis J Neurosci 29 4252 62 2009 19339619 PMC3034143
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The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease
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Microglia in Alzheimer’s disease
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“Relative to the most common apoE3 variant, a single apoE4 or apoE2 allele confers an approximately threefold increased or approximately twofold reduced risk of developing AD, respectively (Corder et al., 1993, 1994; Strittmatter et al., 1993; Farrer et al., 1997).”
BackgroundThe Amyloid-β Pathway in Alzheimer’s Disease
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Microglia in neurodegeneration
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Microglia polarization from M1 to M2 in neurodegenerative diseases
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Self-citationTREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques
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Self-citationTREM2 — a key player in microglial biology and Alzheimer disease
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New insights on the role of microglia in synaptic pruning in health and disease
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Gut microbiota and dysbiosis in Alzheimer's disease: Implications for pathogenesis and treatment
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TREM2 drives microglia response to amyloid-β via SYK-dependent and -independent pathways
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Microglia use TAM receptors to detect and engulf amyloid β plaques
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TREM2, microglia, and neurodegenerative diseases
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White matter aging drives microglial diversity
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TREM2 function impedes tau seeding in neuritic plaques
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Imaging robust microglial activation after lipopolysaccharide administration in humans with PET
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A Path Toward Precision Medicine for Neuroinflammatory Mechanisms in Alzheimer's Disease
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“Besides clearance of Aβ oligomers and fibrils, microglia surrounds plaques and fibrils likely creating a physical barrier that can prevent their spreading and toxicity (61).”
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ApoE facilitates the microglial response to amyloid plaque pathology
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Inhibition of Stat3‐mediated astrogliosis ameliorates pathology in an Alzheimer's disease model
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Microglia Phenotypes in Aging and Neurodegenerative Diseases
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Elucidating the Role of TREM2 in Alzheimer’s Disease
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Innate Immunity and Neurodegeneration
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SYK coordinates neuroprotective microglial responses in neurodegenerative disease
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“Microglia help to limit the spread of pathological Aβ in the brain parenchyma by forming a barrier around Aβ deposits and promoting the physical compaction of Aβ into dense spherical plaques, which ultimately decreases Aβ interaction with susceptible neurons (Condello et al., 2015).”
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Trem2 restrains the enhancement of tau accumulation and neurodegeneration by β-amyloid pathology
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APOE and TREM2 regulate amyloid-responsive microglia in Alzheimer’s disease
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The Trem2 R47H variant confers loss-of-function-like phenotypes in Alzheimer's disease
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Microglia in Brain Development, Homeostasis, and Neurodegeneration
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Cholesterol and Alzheimer’s Disease; From Risk Genes to Pathological Effects
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Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function
Spiteri, A. G., Wishart, C. L., Pamphlett, R., Locatelli, G., & King, N. J. C. (2022) · Acta Neuropathologica · doi:10.1007/s00401-021-02384-2 · Cited by 216 · see citing works
“Neuroprotective roles Microglia encircle Aβ plaques to prevent further growth and dissemination into the parenchyma [63], reducing damage to local neurites [295] Microglia may contribute to the phagocytic and enzymatic clearance of the Aβ plaque deposits [82] TREM2 expressed by damage-associated microglia is thought t…”
BackgroundMeilandt, W. J., Ngu, H., Gogineni, A., Lalehzadeh, G., Lee, S.-H., Srinivasan, K., Imperio, J., Wu, T., Weber, M., Kruse, A. J., et al. (2020) · The Journal of Neuroscience · doi:10.1523/jneurosci.1871-19.2019 · Cited by 210 · see citing works
“3A), these results suggest that the elevated A 42: A 40 ratio in Trem2-deficient brains may increase plaque seeding at younger ages (since A 42 is more prone to aggregate and deposit than A 40) (Klein, 2002) while reducing the incorporation and compaction of A into existing plaques at older ages (since A 40 permeates…”
BackgroundInfluentialTREM2 dependent and independent functions of microglia in Alzheimer’s disease
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Exploiting microglial and peripheral immune cell crosstalk to treat Alzheimer’s disease
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PLD3 affects axonal spheroids and network defects in Alzheimer’s disease
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Self-citationMicroglia limit the expansion of β-amyloid plaques in a mouse model of Alzheimer’s disease
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Alzheimer's-associated PU.1 expression levels regulate microglial inflammatory response
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Microglia-Mediated Neuroprotection, TREM2, and Alzheimer’s Disease: Evidence From Optical Imaging
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Self-citationHypoxia compromises the mitochondrial metabolism of Alzheimer’s disease microglia via HIF1
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APOE genotype and sex affect microglial interactions with plaques in Alzheimer’s disease mice
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TREM2 ectodomain and its soluble form in Alzheimer’s disease
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Microglia and Astrocytes in Alzheimer’s Disease: Significance and Summary of Recent Advances
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- Authors
- Condello, C., Yuan, P., Schain, A., & Grutzendler, J.
- Affiliations
- Yale University (US)
- Corresponding author
- Grutzendler, Jaime
- Venue
- Nature Communications
- Published
- 2015-01-29
- Volume
- 6
- Issue
- 1
- Pages
- 6176-6176
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4311408
- OpenAlex
- W2139976280
- Cited by
- 718
- References
- 65
- Citations by year
- 2026: 68 · 2025: 87 · 2024: 93 · 2023: 98 · 2022: 92 · 2021: 77 · 2020: 63 · 2019: 47 · 2018: 37 · 2017: 27 · 2016: 19 · 2015: 9
- FWCI
- 22.60
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Yale University
- Northwestern University
- University of Toronto
- National Institutes of Health (5r01hl106815-06)
- National Institute on Aging (R21AG048181, R01AG027855, P50AG047270)
- National Heart, Lung, and Blood Institute (R01-HL106815)
- National Institute of Neurological Disorders and Stroke (R21NS087511, R01NS089662, R21NS088411, R01NS089734)
- National Center for Research Resources (S10RR024746)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- Alzheimer's disease, microglia, amyloid plaques, amyloid-beta 42, axonal dystrophy, neuritic dystrophy, CX3CR1, anti-amyloid immunotherapy, aging, neurotoxicity
- MeSH terms
- CX3C Chemokine Receptor 1, Aging, Amyloid, Animals, Astrocytes, Brain, Diffusion, Coloring Agents, Female, Humans, Immunization, Male, Neurotoxins, Peptide Fragments, Solubility, Staining and Labeling, Amyloid beta-Peptides, Neurites, Gene Deletion, Microglia, Neuroprotective Agents, Receptors, Chemokine, Mice, Plaque, Amyloid
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