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38/100

✓ Peer-reviewed alzhub usefulness score 38 out of 100. Inflammation and the immune system

Topic: Brain proteins, microglia and lab models

Abstract Background Dysregulated interferon-alpha/beta-receptor 1 (IFNAR1) signaling was recently identified to contribute to the development of sporadic Parkinson’s disease (PD) into PD with Dementia (PDD). The molecular, cellular, and phenotypic impacts of brain IFNAR1 loss in aging have not been explored in vivo, which may reveal novel disease mechanisms and therapeutic targets. Methods Single nuclei RNA sequencing (snRNA-seq), liquid chromatography tandem mass spectrometry (LC–MS/MS), functional metabolic mapping, flow cytometry, quantitative PCR (qPCR), in situ hybridization, immunofluorescence and immunohistochemistry, Western blotting, and behavior analyses were used to investigate the molecular, cellular, and phenotypic impacts of IFNAR1 loss in vivo . Results Baseline IFNAR1 expression varies among major brain cell types, including neurons and astrocytes, and is differentially affected in PD and Lewy Body Dementia patients compared to unaffected controls. Neuron- and astrocyte-specific transcriptomic and proteomic alterations in Ifnar1 –/– mice implicate mitochondrial defects, defective mitophagy, and synergistic dysfunctional neurotransmission upon IFNAR1 loss, leading to glucose hypermetabolism measured by functional metabolic analysis. Consequently, Ifnar1 –/– mice exhibited PDD-like pathogenesis, including dopaminergic cell loss in the substantia nigra, cortical neurodegeneration, Lewy-body-like inclusions, neuroinflammation, and progressive PDD-like behavior deficits. Brain cell-specific IFNAR1 loss examined in vivo revealed delayed but distinct development of PDD-like phenotypes, where neuropathology, motor, and cognitive behavior deficits were recapitulated only in mice lacking neuronal IFNAR1, and behavior resembling neuropsychiatric abnormalities recapitulated only in mice lacking astrocytic IFNAR1. Conclusions IFNAR1 plays a crucial role in brain and mitochondrial homeostasis, loss of which results in neurodegeneration and neuropathology resembling PDD. Differential neuropathology and behavioral outcomes upon neuronal vs astrocytic IFNAR1 loss emphasizes a need for understanding neurodegenerative pathophysiology in cell-specific contexts. Trial registration Not applicable as the study does not include a clinical trial.

Cite this study APA, Vancouver, BibTeX · download .bib or .ris

APA 7th

Villanueva, E. B., Zebec, Z., Cisquella-Serra, M., Lundstrøm, J., Andersen, J. B., Qvist, F. L., et al. (2026). Distinct and combined interferon-ɑ/β-receptor-1 loss in neurons and astrocytes disrupt brain energy metabolism and drive Parkinsonian dementia. Journal of Biomedical Science. https://doi.org/10.1186/s12929-026-01257-8

Vancouver

Villanueva EB, Zebec Z, Cisquella-Serra M, Lundstrøm J, Andersen JB, Qvist FL, et al. Distinct and combined interferon-ɑ/β-receptor-1 loss in neurons and astrocytes disrupt brain energy metabolism and drive Parkinsonian dementia. Journal of Biomedical Science. 2026. doi:10.1186/s12929-026-01257-8. PMID: 42226039.

BibTeX

@article{villanueva2026-42226039,
  author  = {Villanueva, Erika B. and Zebec, Zala and Cisquella-Serra, Marina and Lundstrøm, Jon and Andersen, JB and Qvist, Filippa Liliendahl and Westi, Emil Winther and Marín, Andrea and others},
  title   = {{Distinct and combined interferon-ɑ/β-receptor-1 loss in neurons and astrocytes disrupt brain energy metabolism and drive Parkinsonian dementia}},
  journal = {Journal of Biomedical Science},
  year    = {2026},
  doi     = {10.1186/s12929-026-01257-8},
  pmid    = {42226039},
  url     = {https://doi.org/10.1186/s12929-026-01257-8}
}

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Key findings

Results Baseline IFNAR1 expression varies among major brain cell types, including neurons and astrocytes, and is differentially affected in PD and Lewy Body Dementia patients compared to unaffected controls.
Brain cell-specific IFNAR1 loss examined in vivo revealed delayed but distinct development of PDD-like phenotypes, where neuropathology, motor, and cognitive behavior deficits were recapitulated only in mice lacking neuronal IFNAR1, and behavior resembling neuropsychiatric abnormalities recapitulated only in mice lacking astrocytic IFNAR1.
Conclusions IFNAR1 plays a crucial role in brain and mitochondrial homeostasis, loss of which results in neurodegeneration and neuropathology resembling PDD.

Why it matters

In mice lacking IFNAR1 in neurons or astrocytes, brain energy metabolism was disrupted and Parkinsonian dementia-like features developed. This is animal research on Parkinson's disease, so it does not provide a treatment or prevention for Alzheimer's disease.

Study details

Evidence strengthLow

How this study scored 38/100

Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (Journal of Biomedical Science)
Journal's citation record	2 / 4	Journal of Biomedical Science: journal h-index 151 (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	5 / 5	2026 — within 1 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	Not stated whether this was studied in people — scores zero (not stated in the record — scored 0)
Randomized / blinded	0 / 2	No randomization or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	1 / 7	Cited 1 times (OpenAlex, 2026-10-10)
Citations per year	0 / 5	0.5 citations a year over 2 year(s) since 2026
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	0 / 6	No other study in this library cites it
Still being cited	0 / 4	Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	2 / 4	Last-listed author Shohreh Issazadeh‐Navikas: h-index 37 (OpenAlex, whole career)
Institution's track record	1 / 3	University of Copenhagen: institution h-index 1,378 (OpenAlex)
Multicenter collaboration	2 / 3	OpenAlex lists 4 institution(s) in 2 countries
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 42226039)
Free to read	2 / 2	Free to read
Total	38 / 100	—

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