Prevention of microgliosis halts early memory loss in a mouse model of Alzheimer’s disease

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline, the neuropathological formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles. The best cellular correlates of the early cognitive deficits in AD patients are synapse loss and gliosis. In particul...
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Autor*in:	Kater, Mandy S.J. [verfasserIn] Huffels, Christiaan F.M. [verfasserIn] Oshima, Takuya [verfasserIn] Renckens, Niek S. [verfasserIn] Middeldorp, Jinte [verfasserIn] Boddeke, Erik W.G.M. [verfasserIn] Smit, August B. [verfasserIn] Eggen, Bart J.L. [verfasserIn] Hol, Elly M. [verfasserIn] Verheijen, Mark H.G. [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	Alzheimer Minocycline Microglia APP/PS1 Microgliosis

Übergeordnetes Werk:	Enthalten in: Brain, behavior and immunity - Orlando, Fla. [u.a.] : Elsevier, 1987, 107, Seite 225-241
Übergeordnetes Werk:	volume:107 ; pages:225-241

DOI / URN:	10.1016/j.bbi.2022.10.009

Katalog-ID:	ELV008913366

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100	1		\|a Kater, Mandy S.J. \|e verfasserin \|4 aut
245	1	0	\|a Prevention of microgliosis halts early memory loss in a mouse model of Alzheimer’s disease
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520			\|a Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline, the neuropathological formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles. The best cellular correlates of the early cognitive deficits in AD patients are synapse loss and gliosis. In particular, it is unclear whether the activation of microglia (microgliosis) has a neuroprotective or pathological role early in AD. Here we report that microgliosis is an early mediator of synaptic dysfunction and cognitive impairment in APP/PS1 mice, a mouse model of increased amyloidosis. We found that the appearance of microgliosis, synaptic dysfunction and behavioral impairment coincided with increased soluble Aβ42 levels, and occurred well before the presence of Aβ plaques. Inhibition of microglial activity by treatment with minocycline (MC) reduced gliosis, synaptic deficits and cognitive impairments at early pathological stages and was most effective when provided preventive, i.e., before the onset of microgliosis. Interestingly, soluble Aβ levels or Aβ plaques deposition were not affected by preventive MC treatment at an early pathological stage (4 months) whereas these were reduced upon treatment at a later stage (6 months). In conclusion, this study demonstrates the importance of early-stage prevention of microgliosis on the development of cognitive impairment in APP/PS1 mice, which might be clinically relevant in preventing memory loss and delaying AD pathogenesis.
650		4	\|a Alzheimer
650		4	\|a Minocycline
650		4	\|a Microglia
650		4	\|a APP/PS1
650		4	\|a Microgliosis
700	1		\|a Huffels, Christiaan F.M. \|e verfasserin \|4 aut
700	1		\|a Oshima, Takuya \|e verfasserin \|4 aut
700	1		\|a Renckens, Niek S. \|e verfasserin \|4 aut
700	1		\|a Middeldorp, Jinte \|e verfasserin \|4 aut
700	1		\|a Boddeke, Erik W.G.M. \|e verfasserin \|4 aut
700	1		\|a Smit, August B. \|e verfasserin \|4 aut
700	1		\|a Eggen, Bart J.L. \|e verfasserin \|4 aut
700	1		\|a Hol, Elly M. \|e verfasserin \|4 aut
700	1		\|a Verheijen, Mark H.G. \|e verfasserin \|0 (orcid)0000-0002-3739-3755 \|4 aut
773	0	8	\|i Enthalten in \|t Brain, behavior and immunity \|d Orlando, Fla. [u.a.] : Elsevier, 1987 \|g 107, Seite 225-241 \|h Online-Ressource \|w (DE-627)254634087 \|w (DE-600)1462491-6 \|w (DE-576)261631098 \|x 1090-2139 \|7 nnns
773	1	8	\|g volume:107 \|g pages:225-241
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912			\|a GBV_ILN_2021
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912			\|a GBV_ILN_4324
912			\|a GBV_ILN_4325
912			\|a GBV_ILN_4326
912			\|a GBV_ILN_4333
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912			\|a GBV_ILN_4335
912			\|a GBV_ILN_4338
912			\|a GBV_ILN_4393
936	b	k	\|a 44.90 \|j Neurologie
951			\|a AR
952			\|d 107 \|h 225-241

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allfields	10.1016/j.bbi.2022.10.009 doi (DE-627)ELV008913366 (ELSEVIER)S0889-1591(22)00414-7 DE-627 ger DE-627 rda eng 610 150 DE-600 44.90 bkl Kater, Mandy S.J. verfasserin aut Prevention of microgliosis halts early memory loss in a mouse model of Alzheimer’s disease 2022 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline, the neuropathological formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles. The best cellular correlates of the early cognitive deficits in AD patients are synapse loss and gliosis. In particular, it is unclear whether the activation of microglia (microgliosis) has a neuroprotective or pathological role early in AD. Here we report that microgliosis is an early mediator of synaptic dysfunction and cognitive impairment in APP/PS1 mice, a mouse model of increased amyloidosis. We found that the appearance of microgliosis, synaptic dysfunction and behavioral impairment coincided with increased soluble Aβ42 levels, and occurred well before the presence of Aβ plaques. Inhibition of microglial activity by treatment with minocycline (MC) reduced gliosis, synaptic deficits and cognitive impairments at early pathological stages and was most effective when provided preventive, i.e., before the onset of microgliosis. Interestingly, soluble Aβ levels or Aβ plaques deposition were not affected by preventive MC treatment at an early pathological stage (4 months) whereas these were reduced upon treatment at a later stage (6 months). In conclusion, this study demonstrates the importance of early-stage prevention of microgliosis on the development of cognitive impairment in APP/PS1 mice, which might be clinically relevant in preventing memory loss and delaying AD pathogenesis. Alzheimer Minocycline Microglia APP/PS1 Microgliosis Huffels, Christiaan F.M. verfasserin aut Oshima, Takuya verfasserin aut Renckens, Niek S. verfasserin aut Middeldorp, Jinte verfasserin aut Boddeke, Erik W.G.M. verfasserin aut Smit, August B. verfasserin aut Eggen, Bart J.L. verfasserin aut Hol, Elly M. verfasserin aut Verheijen, Mark H.G. verfasserin (orcid)0000-0002-3739-3755 aut Enthalten in Brain, behavior and immunity Orlando, Fla. [u.a.] : Elsevier, 1987 107, Seite 225-241 Online-Ressource (DE-627)254634087 (DE-600)1462491-6 (DE-576)261631098 1090-2139 nnns volume:107 pages:225-241 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.90 Neurologie AR 107 225-241
spelling	10.1016/j.bbi.2022.10.009 doi (DE-627)ELV008913366 (ELSEVIER)S0889-1591(22)00414-7 DE-627 ger DE-627 rda eng 610 150 DE-600 44.90 bkl Kater, Mandy S.J. verfasserin aut Prevention of microgliosis halts early memory loss in a mouse model of Alzheimer’s disease 2022 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline, the neuropathological formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles. The best cellular correlates of the early cognitive deficits in AD patients are synapse loss and gliosis. In particular, it is unclear whether the activation of microglia (microgliosis) has a neuroprotective or pathological role early in AD. Here we report that microgliosis is an early mediator of synaptic dysfunction and cognitive impairment in APP/PS1 mice, a mouse model of increased amyloidosis. We found that the appearance of microgliosis, synaptic dysfunction and behavioral impairment coincided with increased soluble Aβ42 levels, and occurred well before the presence of Aβ plaques. Inhibition of microglial activity by treatment with minocycline (MC) reduced gliosis, synaptic deficits and cognitive impairments at early pathological stages and was most effective when provided preventive, i.e., before the onset of microgliosis. Interestingly, soluble Aβ levels or Aβ plaques deposition were not affected by preventive MC treatment at an early pathological stage (4 months) whereas these were reduced upon treatment at a later stage (6 months). In conclusion, this study demonstrates the importance of early-stage prevention of microgliosis on the development of cognitive impairment in APP/PS1 mice, which might be clinically relevant in preventing memory loss and delaying AD pathogenesis. Alzheimer Minocycline Microglia APP/PS1 Microgliosis Huffels, Christiaan F.M. verfasserin aut Oshima, Takuya verfasserin aut Renckens, Niek S. verfasserin aut Middeldorp, Jinte verfasserin aut Boddeke, Erik W.G.M. verfasserin aut Smit, August B. verfasserin aut Eggen, Bart J.L. verfasserin aut Hol, Elly M. verfasserin aut Verheijen, Mark H.G. verfasserin (orcid)0000-0002-3739-3755 aut Enthalten in Brain, behavior and immunity Orlando, Fla. [u.a.] : Elsevier, 1987 107, Seite 225-241 Online-Ressource (DE-627)254634087 (DE-600)1462491-6 (DE-576)261631098 1090-2139 nnns volume:107 pages:225-241 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.90 Neurologie AR 107 225-241
allfields_unstemmed	10.1016/j.bbi.2022.10.009 doi (DE-627)ELV008913366 (ELSEVIER)S0889-1591(22)00414-7 DE-627 ger DE-627 rda eng 610 150 DE-600 44.90 bkl Kater, Mandy S.J. verfasserin aut Prevention of microgliosis halts early memory loss in a mouse model of Alzheimer’s disease 2022 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline, the neuropathological formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles. The best cellular correlates of the early cognitive deficits in AD patients are synapse loss and gliosis. In particular, it is unclear whether the activation of microglia (microgliosis) has a neuroprotective or pathological role early in AD. Here we report that microgliosis is an early mediator of synaptic dysfunction and cognitive impairment in APP/PS1 mice, a mouse model of increased amyloidosis. We found that the appearance of microgliosis, synaptic dysfunction and behavioral impairment coincided with increased soluble Aβ42 levels, and occurred well before the presence of Aβ plaques. Inhibition of microglial activity by treatment with minocycline (MC) reduced gliosis, synaptic deficits and cognitive impairments at early pathological stages and was most effective when provided preventive, i.e., before the onset of microgliosis. Interestingly, soluble Aβ levels or Aβ plaques deposition were not affected by preventive MC treatment at an early pathological stage (4 months) whereas these were reduced upon treatment at a later stage (6 months). In conclusion, this study demonstrates the importance of early-stage prevention of microgliosis on the development of cognitive impairment in APP/PS1 mice, which might be clinically relevant in preventing memory loss and delaying AD pathogenesis. Alzheimer Minocycline Microglia APP/PS1 Microgliosis Huffels, Christiaan F.M. verfasserin aut Oshima, Takuya verfasserin aut Renckens, Niek S. verfasserin aut Middeldorp, Jinte verfasserin aut Boddeke, Erik W.G.M. verfasserin aut Smit, August B. verfasserin aut Eggen, Bart J.L. verfasserin aut Hol, Elly M. verfasserin aut Verheijen, Mark H.G. verfasserin (orcid)0000-0002-3739-3755 aut Enthalten in Brain, behavior and immunity Orlando, Fla. [u.a.] : Elsevier, 1987 107, Seite 225-241 Online-Ressource (DE-627)254634087 (DE-600)1462491-6 (DE-576)261631098 1090-2139 nnns volume:107 pages:225-241 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.90 Neurologie AR 107 225-241
allfieldsGer	10.1016/j.bbi.2022.10.009 doi (DE-627)ELV008913366 (ELSEVIER)S0889-1591(22)00414-7 DE-627 ger DE-627 rda eng 610 150 DE-600 44.90 bkl Kater, Mandy S.J. verfasserin aut Prevention of microgliosis halts early memory loss in a mouse model of Alzheimer’s disease 2022 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline, the neuropathological formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles. The best cellular correlates of the early cognitive deficits in AD patients are synapse loss and gliosis. In particular, it is unclear whether the activation of microglia (microgliosis) has a neuroprotective or pathological role early in AD. Here we report that microgliosis is an early mediator of synaptic dysfunction and cognitive impairment in APP/PS1 mice, a mouse model of increased amyloidosis. We found that the appearance of microgliosis, synaptic dysfunction and behavioral impairment coincided with increased soluble Aβ42 levels, and occurred well before the presence of Aβ plaques. Inhibition of microglial activity by treatment with minocycline (MC) reduced gliosis, synaptic deficits and cognitive impairments at early pathological stages and was most effective when provided preventive, i.e., before the onset of microgliosis. Interestingly, soluble Aβ levels or Aβ plaques deposition were not affected by preventive MC treatment at an early pathological stage (4 months) whereas these were reduced upon treatment at a later stage (6 months). In conclusion, this study demonstrates the importance of early-stage prevention of microgliosis on the development of cognitive impairment in APP/PS1 mice, which might be clinically relevant in preventing memory loss and delaying AD pathogenesis. Alzheimer Minocycline Microglia APP/PS1 Microgliosis Huffels, Christiaan F.M. verfasserin aut Oshima, Takuya verfasserin aut Renckens, Niek S. verfasserin aut Middeldorp, Jinte verfasserin aut Boddeke, Erik W.G.M. verfasserin aut Smit, August B. verfasserin aut Eggen, Bart J.L. verfasserin aut Hol, Elly M. verfasserin aut Verheijen, Mark H.G. verfasserin (orcid)0000-0002-3739-3755 aut Enthalten in Brain, behavior and immunity Orlando, Fla. [u.a.] : Elsevier, 1987 107, Seite 225-241 Online-Ressource (DE-627)254634087 (DE-600)1462491-6 (DE-576)261631098 1090-2139 nnns volume:107 pages:225-241 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.90 Neurologie AR 107 225-241
allfieldsSound	10.1016/j.bbi.2022.10.009 doi (DE-627)ELV008913366 (ELSEVIER)S0889-1591(22)00414-7 DE-627 ger DE-627 rda eng 610 150 DE-600 44.90 bkl Kater, Mandy S.J. verfasserin aut Prevention of microgliosis halts early memory loss in a mouse model of Alzheimer’s disease 2022 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline, the neuropathological formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles. The best cellular correlates of the early cognitive deficits in AD patients are synapse loss and gliosis. In particular, it is unclear whether the activation of microglia (microgliosis) has a neuroprotective or pathological role early in AD. Here we report that microgliosis is an early mediator of synaptic dysfunction and cognitive impairment in APP/PS1 mice, a mouse model of increased amyloidosis. We found that the appearance of microgliosis, synaptic dysfunction and behavioral impairment coincided with increased soluble Aβ42 levels, and occurred well before the presence of Aβ plaques. Inhibition of microglial activity by treatment with minocycline (MC) reduced gliosis, synaptic deficits and cognitive impairments at early pathological stages and was most effective when provided preventive, i.e., before the onset of microgliosis. Interestingly, soluble Aβ levels or Aβ plaques deposition were not affected by preventive MC treatment at an early pathological stage (4 months) whereas these were reduced upon treatment at a later stage (6 months). In conclusion, this study demonstrates the importance of early-stage prevention of microgliosis on the development of cognitive impairment in APP/PS1 mice, which might be clinically relevant in preventing memory loss and delaying AD pathogenesis. Alzheimer Minocycline Microglia APP/PS1 Microgliosis Huffels, Christiaan F.M. verfasserin aut Oshima, Takuya verfasserin aut Renckens, Niek S. verfasserin aut Middeldorp, Jinte verfasserin aut Boddeke, Erik W.G.M. verfasserin aut Smit, August B. verfasserin aut Eggen, Bart J.L. verfasserin aut Hol, Elly M. verfasserin aut Verheijen, Mark H.G. verfasserin (orcid)0000-0002-3739-3755 aut Enthalten in Brain, behavior and immunity Orlando, Fla. [u.a.] : Elsevier, 1987 107, Seite 225-241 Online-Ressource (DE-627)254634087 (DE-600)1462491-6 (DE-576)261631098 1090-2139 nnns volume:107 pages:225-241 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.90 Neurologie AR 107 225-241
language	English
source	Enthalten in Brain, behavior and immunity 107, Seite 225-241 volume:107 pages:225-241
sourceStr	Enthalten in Brain, behavior and immunity 107, Seite 225-241 volume:107 pages:225-241
format_phy_str_mv	Article
bklname	Neurologie
institution	findex.gbv.de
topic_facet	Alzheimer Minocycline Microglia APP/PS1 Microgliosis
dewey-raw	610
isfreeaccess_bool	false
container_title	Brain, behavior and immunity
authorswithroles_txt_mv	Kater, Mandy S.J. @@aut@@ Huffels, Christiaan F.M. @@aut@@ Oshima, Takuya @@aut@@ Renckens, Niek S. @@aut@@ Middeldorp, Jinte @@aut@@ Boddeke, Erik W.G.M. @@aut@@ Smit, August B. @@aut@@ Eggen, Bart J.L. @@aut@@ Hol, Elly M. @@aut@@ Verheijen, Mark H.G. @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
hierarchy_top_id	254634087
dewey-sort	3610
id	ELV008913366
language_de	englisch
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author	Kater, Mandy S.J.
spellingShingle	Kater, Mandy S.J. ddc 610 bkl 44.90 misc Alzheimer misc Minocycline misc Microglia misc APP/PS1 misc Microgliosis Prevention of microgliosis halts early memory loss in a mouse model of Alzheimer’s disease
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title	Prevention of microgliosis halts early memory loss in a mouse model of Alzheimer’s disease
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title_full	Prevention of microgliosis halts early memory loss in a mouse model of Alzheimer’s disease
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author_browse	Kater, Mandy S.J. Huffels, Christiaan F.M. Oshima, Takuya Renckens, Niek S. Middeldorp, Jinte Boddeke, Erik W.G.M. Smit, August B. Eggen, Bart J.L. Hol, Elly M. Verheijen, Mark H.G.
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title_sort	prevention of microgliosis halts early memory loss in a mouse model of alzheimer’s disease
title_auth	Prevention of microgliosis halts early memory loss in a mouse model of Alzheimer’s disease
abstract	Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline, the neuropathological formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles. The best cellular correlates of the early cognitive deficits in AD patients are synapse loss and gliosis. In particular, it is unclear whether the activation of microglia (microgliosis) has a neuroprotective or pathological role early in AD. Here we report that microgliosis is an early mediator of synaptic dysfunction and cognitive impairment in APP/PS1 mice, a mouse model of increased amyloidosis. We found that the appearance of microgliosis, synaptic dysfunction and behavioral impairment coincided with increased soluble Aβ42 levels, and occurred well before the presence of Aβ plaques. Inhibition of microglial activity by treatment with minocycline (MC) reduced gliosis, synaptic deficits and cognitive impairments at early pathological stages and was most effective when provided preventive, i.e., before the onset of microgliosis. Interestingly, soluble Aβ levels or Aβ plaques deposition were not affected by preventive MC treatment at an early pathological stage (4 months) whereas these were reduced upon treatment at a later stage (6 months). In conclusion, this study demonstrates the importance of early-stage prevention of microgliosis on the development of cognitive impairment in APP/PS1 mice, which might be clinically relevant in preventing memory loss and delaying AD pathogenesis.
abstractGer	Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline, the neuropathological formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles. The best cellular correlates of the early cognitive deficits in AD patients are synapse loss and gliosis. In particular, it is unclear whether the activation of microglia (microgliosis) has a neuroprotective or pathological role early in AD. Here we report that microgliosis is an early mediator of synaptic dysfunction and cognitive impairment in APP/PS1 mice, a mouse model of increased amyloidosis. We found that the appearance of microgliosis, synaptic dysfunction and behavioral impairment coincided with increased soluble Aβ42 levels, and occurred well before the presence of Aβ plaques. Inhibition of microglial activity by treatment with minocycline (MC) reduced gliosis, synaptic deficits and cognitive impairments at early pathological stages and was most effective when provided preventive, i.e., before the onset of microgliosis. Interestingly, soluble Aβ levels or Aβ plaques deposition were not affected by preventive MC treatment at an early pathological stage (4 months) whereas these were reduced upon treatment at a later stage (6 months). In conclusion, this study demonstrates the importance of early-stage prevention of microgliosis on the development of cognitive impairment in APP/PS1 mice, which might be clinically relevant in preventing memory loss and delaying AD pathogenesis.
abstract_unstemmed	Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline, the neuropathological formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles. The best cellular correlates of the early cognitive deficits in AD patients are synapse loss and gliosis. In particular, it is unclear whether the activation of microglia (microgliosis) has a neuroprotective or pathological role early in AD. Here we report that microgliosis is an early mediator of synaptic dysfunction and cognitive impairment in APP/PS1 mice, a mouse model of increased amyloidosis. We found that the appearance of microgliosis, synaptic dysfunction and behavioral impairment coincided with increased soluble Aβ42 levels, and occurred well before the presence of Aβ plaques. Inhibition of microglial activity by treatment with minocycline (MC) reduced gliosis, synaptic deficits and cognitive impairments at early pathological stages and was most effective when provided preventive, i.e., before the onset of microgliosis. Interestingly, soluble Aβ levels or Aβ plaques deposition were not affected by preventive MC treatment at an early pathological stage (4 months) whereas these were reduced upon treatment at a later stage (6 months). In conclusion, this study demonstrates the importance of early-stage prevention of microgliosis on the development of cognitive impairment in APP/PS1 mice, which might be clinically relevant in preventing memory loss and delaying AD pathogenesis.
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title_short	Prevention of microgliosis halts early memory loss in a mouse model of Alzheimer’s disease
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author2	Huffels, Christiaan F.M. Oshima, Takuya Renckens, Niek S. Middeldorp, Jinte Boddeke, Erik W.G.M. Smit, August B. Eggen, Bart J.L. Hol, Elly M. Verheijen, Mark H.G.
author2Str	Huffels, Christiaan F.M. Oshima, Takuya Renckens, Niek S. Middeldorp, Jinte Boddeke, Erik W.G.M. Smit, August B. Eggen, Bart J.L. Hol, Elly M. Verheijen, Mark H.G.
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up_date	2024-07-06T21:20:23.928Z
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