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Age-dependent neuroinflammation and cognitive decline in a novel Ala152Thr-Tau transgenic mouse model of PSP and AD
Sydow A, Hochgräfe K, Könen S, Cadinu D, Matenia D, Petrova O, Joseph M, Dennissen FJ et al.. Acta neuropathologica communications, 2016-02-25
Topic: Brain proteins, microglia and lab models
Introduction Mutations of Tau are associated with several neurodegenerative disorders. Recently, the Tau mutation A152T was described as a novel risk factor for frontotemporal dementia spectrum disorders and Alzheimer disease. In vitro Tau-A152T shows a decreased binding to microtubules and a reduced tendency to form abnormal fibers. Results To study the effects of this mutation we generated a mouse model expressing human full-length Tau with this mutation (hTau40(AT)). At young age (2-3 months) immunohistological analysis reveals pathological Tau conformation and Tau-hyperphosphorylation combined with Tau missorting into the somatodendritic compartment of neurons. With increasing age there is Tau aggregation including co-aggregates of endogenous mouse Tau and exogenous human Tau, accompanied by loss of synapses (especially presynaptic failure) and neurons. From ~10 months onwards the mice show a prominent neuroinflammatory response as judged by activation of microglia and astrocytes. This progressive neuroinflammation becomes visible by in vivo bioluminescence imaging after crossbreeding of hTau40(AT) mice and Gfap-luciferase reporter mice. In contrast to other Tau-transgenic models and Alzheimer disease patients with reduced protein clearance, hTau40(AT) mice show a strong induction of autophagy. Although Tau-hyperphosphorylation and aggregation is also present in spinal cord and motor cortex (due to the Thy1.2 promoter), neuromotor performance is not affected. Deficits in spatial reference memory are manifest at ~16 months and are accompanied by neuronal death. Conclusions The hTau40(AT) mice mimic pathological hallmarks of tauopathies including a cognitive phenotype combined with pronounced neuroinflammation visible by bioluminescence. Thus the mice are suitable for mechanistic studies of Tau induced toxicity and in vivo validation of neuroprotective compounds.
Key findings
- Introduction Mutations of Tau are associated with several neurodegenerative disorders.
- Results To study the effects of this mutation we generated a mouse model expressing human full-length Tau with this mutation (hTau40(AT)).
Why it matters
A new mouse model carrying the Tau A152T mutation developed tau pathology, synapse and neuron loss, neuroinflammation and cognitive decline with age. This is a mouse model describing how a risk mutation may cause damage, not evidence of any treatment, cure or prevention in humans.
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Study details
- Evidence strengthLow
How this study scored 42/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Acta neuropathologica communications) |
| Journal's citation record | 1 / 4 | Acta Neuropathologica Communications: journal h-index 129 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2016 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “transgenic”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 43 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.6 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 3 / 6 | Cited 4.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 5 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Eva‐Maria Mandelkow: h-index 122 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Max Planck Society: institution h-index 1,183 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 26916334) |
| Free to read | 2 / 2 | Free to read |
| Total | 42 / 100 | — |
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Read the original
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APA 7th
Sydow, A., Hochgräfe, K., Könen, S., Cadinu, D., Matenia, D., Petrova, O., et al. (2016). Age-dependent neuroinflammation and cognitive decline in a novel Ala152Thr-Tau transgenic mouse model of PSP and AD. Acta neuropathologica communications. https://doi.org/10.1186/s40478-016-0281-z
Vancouver
Sydow A, Hochgräfe K, Könen S, Cadinu D, Matenia D, Petrova O, et al. Age-dependent neuroinflammation and cognitive decline in a novel Ala152Thr-Tau transgenic mouse model of PSP and AD. Acta neuropathologica communications. 2016. doi:10.1186/s40478-016-0281-z. PMID: 26916334.
BibTeX
@article{sydow2016-26916334,
author = {Sydow, A. and Hochgräfe, K. and Könen, S. and Cadinu, D. and Matenia, D. and Petrova, O. and Joseph, M. and Dennissen, F. J. and others},
title = {{Age-dependent neuroinflammation and cognitive decline in a novel Ala152Thr-Tau transgenic mouse model of PSP and AD}},
journal = {Acta neuropathologica communications},
year = {2016},
doi = {10.1186/s40478-016-0281-z},
pmid = {26916334},
url = {https://doi.org/10.1186/s40478-016-0281-z}
}
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