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Spatiotemporal transcriptomic dynamic across the auditory pathway from young to old age in 5xFAD Alzheimer disease mice
Kong Y, Zhai T, Zhao H.. bioRxiv, 2026-10-18
Topic: Genetics and APOE
Auditory dysfunction can precede clinical dementia, but the molecular progression of Alzheimer disease (AD) pathology from the sensory periphery to auditory cortex remains poorly resolved. We performed bulk RNA sequencing of auditory cortex (AC), inferior colliculus (IC), cochlear nucleus (CN), and cochlea from 5xFAD and wild-type mice at postnatal day 50 (P50), 8 months, 11 months, and 16 months. Age-specific genotype effects and Genotype×Age interactions were evaluated using DESeq2, followed by Hallmark, KEGG, and Gene Ontology gene-set enrichment analyses and a cross-region synthesis of interaction trajectories. At P50, AC, IC, and cochlea showed coordinated suppression of mitochondrial metabolism, translation, RNA processing, and proteostasis, whereas CN displayed the opposite metabolic and biosynthetic profile together with reduced synaptic and adhesion programs. At 8 months, inflammatory interactions converged across all four regions, including interferon, complement, IL6–JAK–STAT3, and broader immune-response pathways. This coordination fractured at 11 months: AC and IC retained inflammatory and negative synaptic shifts, whereas CN and cochlea frequently changed in the opposite direction, including transient positive shifts in synaptic programs. By 16 months, immune interactions converged again, while metabolic, proteostatic, and synaptic trajectories remained region dependent; CN opposed AC, IC, and cochlea in several major metabolic programs. These findings define a distributed, asynchronous response rather than a monotonic bottom-up or top-down progression. The resulting spatiotemporal map links early metabolic stress, intermediate central–peripheral decoupling, and late inflammatory convergence, providing a molecular framework for evaluating peripheral-to-central auditory gain and temporal-processing measures as candidate indicators of AD progression.
Key findings
- These findings define a distributed, asynchronous response rather than a monotonic bottom-up or top-down progression.
Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| 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 | Laboratory or animal study (title names “5xfad”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
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APA 7th
Kong, Y., Zhai, T., & Zhao, H. (2026). Spatiotemporal transcriptomic dynamic across the auditory pathway from young to old age in 5xFAD Alzheimer disease mice. bioRxiv. https://doi.org/10.64898/2026.10.17.759861
Vancouver
Kong Y, Zhai T, Zhao H. Spatiotemporal transcriptomic dynamic across the auditory pathway from young to old age in 5xFAD Alzheimer disease mice. bioRxiv. 2026. doi:10.64898/2026.10.17.759861.
BibTeX
@article{kong2026-36e22c46,
author = {Kong, Y. and Zhai, T. and Zhao, H.},
title = {{Spatiotemporal transcriptomic dynamic across the auditory pathway from young to old age in 5xFAD Alzheimer disease mice}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.10.17.759861},
url = {https://doi.org/10.64898/2026.10.17.759861}
}