Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model
Open accessAbstract
Filamentous tau inclusions are hallmarks of Alzheimer's disease (AD) and related tauopathies, but earlier pathologies may herald disease onset. To investigate this, we studied wild-type and P301S mutant human tau transgenic (Tg) mice. Filamentous tau lesions developed in P301S Tg mice at 6 months of age, and progressively accumulated in association with striking neuron loss as well as hippocampal and entorhinal cortical atrophy by 9-12 months of age. Remarkably, hippocampal synapse loss and impaired synaptic function were detected in 3 month old P301S Tg mice before fibrillary tau tangles emerged. Prominent microglial activation also preceded tangle formation. Importantly, immunosuppression of young P301S Tg mice with FK506 attenuated tau pathology and increased lifespan, thereby linking neuroinflammation to early progression of tauopathies. Thus, hippocampal synaptic pathology and microgliosis may be the earliest manifestations of neurodegenerative tauopathies, and abrogation of tau-induced microglial activation could retard progression of these disorders.
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Microglia activation precedes tau aggregation and promotes tau hyperphosphorylation, subsequently leading to formation of NFTs.
“since activation of microglia precedes tau aggregation41 and promotes tau hyperphosphorylation which subsequently leads to the formation of NFTs.42”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [41]
Neuroinflammation is an early feature of pathophysiology in mouse models of tauopathy, where inflammatory changes precede the accumulation of aggregated tau, and pro-inflammatory molecules increase tau hyperphosphorylation and aggregation.
“Neuroinflammation is an early feature of pathophysiology in mouse models of tauopathy, where inflammatory changes precede the accumulation of aggregated tau (Yoshiyama et al., 2007) and pro-inflammatory molecules increase tau hyperphosphorylation and aggregation (Bhaskar et al., 2010).”
From Neuroinflammation and protein aggregation co-localize across the frontotemporal dementia spectrum (2020) · cites this paper as Yoshiyama et al., 2007
The study used 9-month-old animals, when each model exhibits robust amyloid and/or tau pathology, and included equal numbers of males and females.
“We used 9‐month‐old animals, when each model exhibits robust amyloid and/or tau pathology, 11 , 12 , 43 and included equal numbers of males and females.”
From Unique transcriptomic alterations in 5XFAD;PS19 mouse model identify glial lipid dysregulation and coordinated microglial–oligodendrocyte responses (2026) · cites this paper as [12]
PS19 mice exhibit age-dependent accumulation of pTau, microgliosis, and neurodegeneration from 3 to 9 months of age, resulting in a shortened life span (9-12 months of age).
“Whereas PS19 mice exhibit age-dependent accumulation of pTau, microgliosis, and neurodegeneration from 3 to 9 months of age, resulting in a shortened life span in this model (9–12 months of age) (Yoshiyama et al. 2007)”
From Perineuronal net deglycosylation associates with tauopathy‐induced gliosis and neurodegeneration (2024) · cites this paper as Yoshiyama et al. 2007
Neurodegeneration is a hallmark of AD in both demented patients and aged PS19 mice.
“Neurodegeneration is a hallmark of AD in both demented patients and aged PS19 mice (Yoshiyama et al. 2007; Terry et al. 1991).”
From Perineuronal net deglycosylation associates with tauopathy‐induced gliosis and neurodegeneration (2024) · cites this paper as Yoshiyama et al. 2007
3-month-old PS19 mice do not exhibit pTau accumulation.
“Whereas 3-month-old PS19 mice do not exhibit pTau accumulation (Yoshiyama et al. 2007)”
From Perineuronal net deglycosylation associates with tauopathy‐induced gliosis and neurodegeneration (2024) · cites this paper as Yoshiyama et al. 2007
Both pTau accumulation and increased gliosis observed in 9m-PS19 mice may play a role in neurodegeneration within the DG, potentially contributing to the cognitive deficits often observed in this AD mouse model.
“These data suggest that both pTau accumulation and increased gliosis observed in 9m-PS19 mice may play a role in neurodegeneration within the DG, potentially contributing to the cognitive deficits often observed in this AD mouse model (Yoshiyama et al. 2007).”
From Perineuronal net deglycosylation associates with tauopathy‐induced gliosis and neurodegeneration (2024) · cites this paper as Yoshiyama et al. 2007
PS19 mice overexpress P301S mutant human tau and develop progressive accumulation of hyperphosphorylated and insoluble tau protein.
“PS19 mice, which overexpress P301S mutant human tau and develop progressive accumulation of hyperphosphorylated and insoluble tau protein (Yoshiyama et al., 2007).”
From Spontaneous pathology in PS19 tauopathy mice progresses via brain networks (2025) · cites this paper as Yoshiyama et al., 2007
Cluster C1 contained five 6mo brains and a 9mo brain.
“The cluster with lowest overall p-tau intensity (Fig. 5A, “C1”) contained five 6mo brains, when consistent pathology emerges in the PS19 model (Yoshiyama et al., 2007; Holmes et al., 2014), as well as a 9mo brain.”
From Spontaneous pathology in PS19 tauopathy mice progresses via brain networks (2025) · cites this paper as Yoshiyama et al., 2007
The patterns of labeling of Aβ and MAPT are consistent with prior studies of APPNL-G-F and P301S MAPT mice.
“These patterns of labeling or Aβ and MAPT are consistent with prior studies of APPNL-G-F and P301S MAPT mice (Yoshiyama et al., 2007; Saito et al., 2014; Sasaguri et al., 2017; Apicco et al., 2018).”
From β-amyloid accumulation enhances microtubule associated protein tau pathology in an APPNL-G-F/MAPTP301S mouse model of Alzheimer’s disease (2024) · cites this paper as Yoshiyama et al., 2007
MAPT pathology in the MAPTP301S model accumulates rapidly because of the strong MAPT expression (the human protein is expressed about 5-fold higher than the endogenous mouse protein) and the protein itself has a mutation that enhances the rate of aggregation.
“MAPT pathology in the MAPTP301S model accumulates so rapidly because of the strong MAPT expression (the human protein is expressed about 5-fold higher than the endogenous mouse protein) and the protein itself has a mutation that enhances the rate of aggregation (Yoshiyama et al., 2007).”
From β-amyloid accumulation enhances microtubule associated protein tau pathology in an APPNL-G-F/MAPTP301S mouse model of Alzheimer’s disease (2024) · cites this paper as Yoshiyama et al., 2007
The PS19 tau transgenic model overexpresses tau with the P301S mutation.
“We generated double-transgenic mice by crossbreeding homozygous Tg4–42 mice with the widely used PS19 tau transgenic model overexpressing tau with the P301S mutation [26] and performed behavioral and neuropathological analysis at different time points.”
From Characterization of a Mouse Model of Alzheimer’s Disease Expressing Aβ4-42 and Human Mutant Tau (2021) · cites this paper as [26]
The PS19 line did not show any difference compared to WT mice in either the distal or proximal region of CA1 at the considered time points.
“At the considered time points, the PS19 line did not show any difference compared to WT mice, neither in the distal nor proximal region of CA1 (Figure 4c–h), in good agreement with previous findings showing no hippocampal neuron loss in this model until 9–12 months [26].”
From Characterization of a Mouse Model of Alzheimer’s Disease Expressing Aβ4-42 and Human Mutant Tau (2021) · cites this paper as [26]
Neuron loss in the CA3 and reduced DG volume have been described in P301S mice starting at 8 months.
“The tau transgenic line did not present with loss of CA1 pyramidal neurons at the considered time points, but neuron loss in the CA3 and reduced DG volume have been described in P301S mice starting at 8 months [26,43].”
From Characterization of a Mouse Model of Alzheimer’s Disease Expressing Aβ4-42 and Human Mutant Tau (2021) · cites this paper as [26]
PS19 mice overexpress human tau with the P310S mutation under the control of the murine prion protein promoter.
“PS19 mice overexpress human tau with the P310S mutation under the control of the murine prion protein promoter [26] and were purchased from Jackson laboratories (Bar Harbor, ME, USA) (B6;C3-Tg(Prnp-MAPT*P301S)PS19Vle/J).”
From Characterization of a Mouse Model of Alzheimer’s Disease Expressing Aβ4-42 and Human Mutant Tau (2021) · cites this paper as [26]
DTI microstructural changes seem to precede gross anatomical changes seen on structural MRI.
“Importantly, DTI microstructural changes seem to precede gross anatomical changes seen on structural MRI [24].”
From Diffusion tensor imaging reveals whole-brain microstructural changes in the P301L mouse model of tauopathy. (2020) · cites this paper as [24]
The observed pattern of decreased FA and increased MD, RD, and AD in P301L mice is in good agreement with DTI changes observed in human tauopathies such as progressive supranuclear palsy, frontotemporal dementia, mild cognitive impairment, and Alzheimer's disease.
“In this regard, the observed pattern of decreased FA and increased MD, RD, and AD values in P301L mice in the current study are in good agreement with DTI changes observed in human tauopathies such as progressive supranuclear palsy [21], frontotemporal dementia [22], mild cognitive impairment [24], and Alzheimer`s disease [18,25].”
From Diffusion tensor imaging reveals whole-brain microstructural changes in the P301L mouse model of tauopathy. (2020) · cites this paper as [24]
Studies in patients with mild cognitive impairment have shown that changes in DTI metrics in the hippocampus can predict cognitive decline and constitute a more sensitive predictor than changes in hippocampal volume.
“Studies in patients with mild cognitive impairment have shown that changes in DTI metrics in the hippocampus, a region involved in working memory formation can predict cognitive decline and constitute a more sensitive predictor than changes in hippocampal volume [24].”
From Diffusion tensor imaging reveals whole-brain microstructural changes in the P301L mouse model of tauopathy. (2020) · cites this paper as [24]
Tau expression levels in this study were higher than endogenous levels but equivalent to the levels of tau transgene in PS19 mice.
“The levels of tau expression in our study, while higher than endogenous levels, were equivalent to the levels of tau transgene in the PS19 mice which are widely used for studying tauopathy (40).”
From Combinatorial model of amyloid β and tau reveals synergy between amyloid deposits and tangle formation (2022) · cites this paper as [40]
Transgenic mice expressing human mutated tau showed NFT formation and neuronal loss, implying a causal relationship between tau over-expression and neurodegeneration.
“transgenic mice expressing human mutated tau showed NFT formation and neuronal loss, implying a causal relationship between tau over-expression and neurodegeneration (8 -11).”
No significant difference in AT8+ area coverage was observed between PS19 and PS19;ApoeCh mice at both 5 and 9 mo of age.
“However, no significant difference was observed between PS19 and PS19;ApoeCh mice at both 5 and 9 mo of age (Fig. 5a-d, Supp. Figure 14a-c) [45, 67–69].”
From APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology (2025) · cites this paper as [45]
Both models rely on transgene overexpression and familial mutations and are not well suited for studying causative events that lead to development of pathology in sporadic AD.
“Both models rely on transgene overexpression and familial mutations (such as ADAD mutations in 5xFAD mice and frontotemporal dementia mutations in PS19 mice) and are not well suited for studying the causative events that lead to the development of pathology in sporadic AD [44–47].”
From APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology (2025) · cites this paper as [45]
Tau pathology can interfere with neuronal circuits, resulting in theta and gamma oscillation deficits long before neurons die.
“Previous studies have shown that tau pathology can interfere with neuronal circuits, resulting in theta and gamma oscillation deficits long before neurons die16,20–23.”
From The R136S mutation in the APOE3 gene confers resilience against tau pathology via inhibition of the cGAS-STING-IFN pathway (2025) · cites this paper as [16]
PS19 transgenic mice express human tau with the P301S mutation and display neurofibrillary tangles at 6 months of age followed by progressive hippocampal and cortical atrophy at 9-12 months of age.
“we employed the PS19 transgenic mice which express the human tau protein containing the P301S mutation associated with frontotemporal dementia (FTD) and display NFTs at 6 months of age followed by progressive hippocampal and cortical atrophy at 9-12 months of age (Yoshiyama et al., 2007).”
From APOE4 reduces hippocampal expression of phosphoglycerate kinase 1 and sodium potassium pump to enhance seizure susceptibility in mice (2026) · cites this paper as Yoshiyama et al., 2007
NFT-like tau inclusions have been reported in 6-month-old PS19 mice in both the hippocampus and prelimbic prefrontal cortex, with neuronal loss becoming evident at 9 months of age.
“NFT-like tau inclusions have been reported in 6 month old PS19 mice, in both the hippocampus and prelimbic prefrontal cortex, with neuronal loss becoming evident at 9 months of age (Yoshiyama et al., 2007).”
From Dendritic Spine Remodeling and Synaptic Tau Levels in PS19 Tauopathy Mice (2021) · cites this paper as Yoshiyama et al., 2007
Tau, including phosphorylated tau, is present in presynaptic and postsynaptic compartments in the PS19 mouse model.
“Tau, including phosphorylated tau, is present in presynaptic and postsynaptic compartments in the PS19 mouse model (Yoshiyama et al., 2007, Dejanovic et al., 2018, McInnes et al., 2018).”
From Dendritic Spine Remodeling and Synaptic Tau Levels in PS19 Tauopathy Mice (2021) · cites this paper as Yoshiyama et al., 2007
Synaptophysin, a presynaptic marker, was used for synapse quantification in two of the past studies.
“Furthermore, synaptophysin, a presynaptic marker, was used for synapse quantification in two of the studies (Yoshiyama et al., 2007, Crescenzi et al., 2014), whereas our methods assess the postsynaptic dendritic spine.”
From Dendritic Spine Remodeling and Synaptic Tau Levels in PS19 Tauopathy Mice (2021) · cites this paper as Yoshiyama et al., 2007
The PS19 mouse line overexpresses 1N4R human tau with the frontotemporal dementia-associated P301S mutation under the control of the mouse prion protein promoter.
“The PS19 mouse line overexpresses 1N4R human tau with the frontotemporal dementia-associated P301S mutation under the control of the mouse prion protein promoter (Yoshiyama et al., 2007).”
From Dendritic Spine Remodeling and Synaptic Tau Levels in PS19 Tauopathy Mice (2021) · cites this paper as Yoshiyama et al., 2007
PS19 mice exhibit deficits in synaptic function, including impaired long-term potentiation in CA1 of the hippocampus.
“Moreover, despite the lack of robust spine loss observed in this study, PS19 mice exhibit deficits in synaptic function, including impaired long-term potentiation in CA1 of the hippocampus (Yoshiyama et al., 2007).”
From Dendritic Spine Remodeling and Synaptic Tau Levels in PS19 Tauopathy Mice (2021) · cites this paper as Yoshiyama et al., 2007
In PS19 mice, there were no robust differences in spine density when PS19 mice were compared to NTG littermates, despite reported behavioral and electrophysiological deficits at the ages assessed.
“Although behavioral and electrophysiological deficits have been reported in the PS19 line at the ages assessed in our study (Yoshiyama et al., 2007, Takeuchi et al., 2011, Briggs et al., 2017, Chalermpalanupap et al., 2018), we did not observe robust differences in spine density when PS19 mice were compared to NTG littermates.”
From Dendritic Spine Remodeling and Synaptic Tau Levels in PS19 Tauopathy Mice (2021) · cites this paper as Yoshiyama et al., 2007
Soluble tau, rather than NFTs, is the pathologic tau species.
“Given the evidence that soluble tau, rather than NFTs, is the pathologic tau species (Santacruz et al., 2005, Yoshiyama et al., 2007, Kopeikina et al., 2012, Lasagna-Reeves et al., 2012, Polydoro et al., 2014, Ghag et al., 2018)”
From Dendritic Spine Remodeling and Synaptic Tau Levels in PS19 Tauopathy Mice (2021) · cites this paper as Yoshiyama et al., 2007
Past studies that reported synapse loss in PS19 mice relied on immunohistochemical staining of synaptic markers, which does not yield image resolution comparable to the methods employed here.
“However, these studies relied on immunohistochemical staining of synaptic markers, which does not yield image resolution that is comparable to the methods employed here.”
From Dendritic Spine Remodeling and Synaptic Tau Levels in PS19 Tauopathy Mice (2021) · cites this paper as Yoshiyama et al., 2007
NFT-like inclusions are already present in PS19 mice at 6 months.
“and the fact that NFT-like inclusions are already present in PS19 mice at 6 months (Yoshiyama et al., 2007)”
From Dendritic Spine Remodeling and Synaptic Tau Levels in PS19 Tauopathy Mice (2021) · cites this paper as Yoshiyama et al., 2007
Radiograms utilizing [3H]DAA1106 demonstrated age-dependent microglial activation in the hippocampus, amygdala and entorhinal cortex.
“Additional radiograms utilizing [3H]DAA1106 clearly demonstrated an age-dependent microglial-activation in the hippocampus, amygdala and entorhinal cortex.”
From Glial contributions to neurodegeneration in tauopathies (2017) · cites this paper as [115]
Yoshiyama et al. provided the most compelling evidence to date that microgliosis can precede tau tangle formation and is capable of driving neurodegeneration.
“Yoshiyama et al. has provided the most compelling evidence to date that microgliosis can precede tau tangle formation and is capable of driving neurodegeneration.”
From Glial contributions to neurodegeneration in tauopathies (2017) · cites this paper as [115]
Treatment of PS19 mice with the immunosuppressant FK506 beginning at 2 months of age significantly reduced tau pathology and brain atrophy and dramatically increased life-span.
“the immunosuppressant FK506 was given to the mice beginning at 2 months of age. Not only did treatment significantly reduce tau pathology and brain atrophy, it dramatically increased the life-span of the mice.”
From Glial contributions to neurodegeneration in tauopathies (2017) · cites this paper as [115]
CA3 neurons in the hippocampus of 4-month-old PS19 mice were immunoreactive for IL-β and COX-2.
“Moreover, CA3 neurons in the hippocampus of 4-month-old mice were immunoreactive for IL-β and COX-2.”
From Glial contributions to neurodegeneration in tauopathies (2017) · cites this paper as [115]
In the initial PS19 tau transgenic mouse paper, a striking increase in CD11b immunoreactivity was observed in 3-month-old animals prior to the accumulation of tau deposits.
“In their initial paper describing the PS19 tau transgenic mouse, the authors were surprised by the striking increase in CD11b immunoreactivity in 3-month-old animals, prior to the accumulation of tau deposits [115].”
From Glial contributions to neurodegeneration in tauopathies (2017) · cites this paper as [115]
Proinflammatory microglia precede visible tau pathology in transgenic mice; FK506 attenuates their activation, tau pathology, and extends lifespan, suggesting microglia mediate tau neurotoxicity.
“Proinflammatory microglia precede visible tau pathology in transgenic mice, and their activation is attenuated by the immunosuppressant drug FK506, which attenuates tau pathology and extends lifespan in these mice, suggesting that microglia can mediate tau neurotoxicity54.”
From Microglia in neurodegeneration (2018) · cites this paper as [54]
Immunosuppression with FK506 significantly decreased tau pathology and increased lifespan in young P301S Tg mice, demonstrating that microglial activation and neuroinflammation promoted the early progression of tauopathies.
“Importantly, immunosuppression with FK506 significantly decreased tau pathology and increased lifespan in young P301S Tg mice, thereby demonstrating that microglial activation and neuroinflammation promoted the early progression of tauopathies.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [395]
Pre-clinical research suggests that microglial activation may precede tangle formation and promote the spreading of pathological tau.
“Pre-clinical research suggests that microglial activation may precede the formation of tangles47 and then promote the spreading of pathological tau48.”
From Neuroinflammation and Tau Colocalize in vivo in Progressive Supranuclear Palsy (2020) · cites this paper as [47]
In MAPT mutations, mutant tau misfolding might initiate neuroinflammation, which could then promote tau hyperphosphorylation and aggregation.
“In patients with MAPT mutations, neuroinflammation may be triggered by the misfolding of mutant tau and contribute to its hyperphosphorylation and aggregation[4,14,16], while in C9orf72 and GRN cases, neuroinflammation could be triggered by dipeptide repeats or progranulin haploinsufficiency in advance of the large TDP-43 aggregates[14,17].”
From In vivo PET imaging of neuroinflammation in familial frontotemporal dementia (2021) · cites this paper as [4]
In 9-month PS19 mice, neuronal numbers are reduced in both CA1 and CA3 areas of hippocampus.
“In agreement with a previous report (Yoshiyama et al., 2007), unbiased stereology showed reduced neuronal numbers in both CA1 and CA3 areas of the hippocampus in 9-month-old PS19 mice (Figures 4G and 4H; Figures S3K and S3L).”
From Complement C3aR Inactivation Attenuates Tau Pathology and Reverses an Immune Network Deregulated in Tauopathy Models and Alzheimer’s Disease (2018) · cites this paper as Yoshiyama et al., 2007
Microglial activation precedes tau pathology in a tauopathy mouse model.
“Microglial activation is shown to precede tau pathology in a tauopathy mouse model58”
From Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight (2018) · cites this paper as [58]
Administering an immunosuppressant drug FK506 from an early age drastically reduces tau pathology, neurodegeneration and mortality in a tauopathy mouse model.
“administering an immunosuppressant drug FK506 from an early age drastically reduces tau pathology, neurodegeneration and mortality58.”
From Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight (2018) · cites this paper as [58]
The correlation between inflammation and tangle formation has also been noted in other tauopathies, such as frontotemporal dementia and chronic traumatic encephalopathy.
“The correlation between inflammation and tangle formation has also been noted in other tauopathies, such as frontotemporal dementia and chronic traumatic encephalopathy [42–45].”
From Deep proteomic network analysis of Alzheimer’s disease brain reveals alterations in RNA binding proteins and RNA splicing associated with disease (2018) · cites this paper as [45]
NFTs readily form in transgenic mice that express human tau containing mutations associated with FTLD; the most commonly used models express 4R tau with P301L or P301S mutations.
“In contrast, NFTs readily form in transgenic mice that express human tau containing mutations associated with FTLD; the most commonly used models being those that express 4R tau with P301L or P301S mutations[49, 91, 92, 135, 177].”
From Alzheimer's disease: experimental models and reality (2017) · cites this paper as [177]
The study's findings are restricted to the PS19 mouse model of tauopathy.
“While we predict that lowering tau with antisense oligonucleotides in any tauopathy model would show similar benefit, our study here was restricted to the PS19 mouse model of tauopathy (16).”
From Tau reduction prevents neuronal loss and reverses pathological tau deposition and seeding in mice with tauopathy (2017) · cites this paper as [16]
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- Authors
- Yoshiyama, Y., Higuchi, M., Zhang, B., Huang, S.-M., Iwata, N., Saido, T. C., Maeda, J., Suhara, T., Trojanowski, J. Q., & Lee, V. M.-Y.
- Affiliations
- Chiba East Hospital (JP)
- RIKEN Center for Brain Science (JP)
- University of Pennsylvania (US)
- National Institute of Radiological Sciences (JP)
- Corresponding author
- Lee, Virginia M.-Y.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2007-02
- Volume
- 53
- Issue
- 3
- Pages
- 337-351
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2057249855
- Cited by
- 2,208
- References
- 63
- Citations by year
- 2026: 138 · 2025: 216 · 2024: 180 · 2023: 210 · 2022: 180 · 2021: 161 · 2020: 166 · 2019: 107 · 2018: 126 · 2017: 99 · 2016: 96 · 2015: 85 · 2014: 90 · 2013: 69 · 2012: 59
- FWCI
- 34.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- Funders
- University of Pennsylvania
- Astellas Foundation for Research on Metabolic Disorders
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- tauopathy, Alzheimer's disease, synaptic loss, microglial activation, tau tangles, hippocampal atrophy, entorhinal cortex, neuroinflammation, transgenic mouse model, early neurodegeneration, lifespan extension
- MeSH terms
- Aging, Amygdala, Animals, Atrophy, Brain, Gliosis, Humans, Immunohistochemistry, Immunosuppressive Agents, Macrophage Activation, Microscopy, Electron, Microtubules, Nerve Degeneration, Phosphorylation, Solubility, Spinal Cord, Synapses, Blotting, Western, Tacrolimus, Neurofibrillary Tangles, tau Proteins, Microglia, Amyloid Neuropathies, Mossy Fibers, Hippocampal, Mice
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