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Chronic Ethanol Causes Persistent Increases in Alzheimer's Tau Pathology in Female 3xTg-AD Mice: A Potential Role for Lysosomal Impairment
Tucker AE, Alicea Pauneto CDM, Barnett AM, Coleman LG.. Frontiers in behavioral neuroscience, 2022-05-11
Topic: Brain proteins, microglia and lab models
Epidemiological studies have found that heavy alcohol use is associated with increased risk for Alzheimer's disease (AD), with frequent drinking earlier in adulthood increasing risk. The increases in neuroinflammation featured in both heavy alcohol use and AD may be partially responsible for this link. However, it is unknown if abstinence mitigates this risk. We hypothesized that binge ethanol during mid adult life would persistently increase AD pathology even after prolonged abstinence. Male and female 3xTg-AD mice (APPSwe, tauP301, Psen1 tm1Mpm ) which feature progressive amyloid (Aβ) and tau pathology, received chronic binge ethanol (5g/kg/day, 5-days-on/2-days-off, i.g.) or water during adulthood (from 5.5 to 9 months of age), followed by abstinence and assessment at 14 months of age. The effects of ethanol on protective AD genes (e.g., APOE and TREM2) as well as proinflammatory genes were measured by PCR. Levels of pathologic tau and Aβ were measured by immunohistochemistry and western blot. Ethanol caused persistent reductions in protective AD genes: APOE (25% reduction, * p < 0.05), TREM2 (28%, * p < 0.05), LPL (40%, ** p < 0.01), and CTSD (24%, * p < 0.05) and promoted a proinflammatory gene signature in female, but not male cortex. Concurrently, ethanol increased total and hyperphosphorylated tau (AT8) in piriform cortex and hippocampus of females, but not males. Levels of AT8 were negatively correlated with APOE ( R = -0.67, * p < 0.05) and TREM2 ( R = -0.78, ** p < 0.005) suggesting protective roles in pathogenesis. No differences were found in levels of main regulators of tau phosphorylation state (GSK3β, PKA, PP2A), suggesting ethanol disrupted clearance of tau. Therefore, we measured the effect of ethanol on lysosomes, which degrade tau, and lysosomal localization of tau using co-immunofluorescence. In females, ethanol caused a persistent reduction in mature LAMP1 lysosomes in CA1 of hippocampus (35%, * p < 0.05), along with a 60% increase in total tau (* p < 0.05). Thus, chronic binge ethanol during mid adult life causes a persistent enhancement of tau pathology in cortical and hippocampal brain regions of females. Persistent AD pathology was associated with an increased proinflammatory signature and a reduction of mature lysosomes. This implicates binge ethanol exposure with increased risk of AD pathologic progression in females.
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APA 7th
Tucker, A. E., Alicea Pauneto, C. D. M., Barnett, A. M., & Coleman, L. G. (2022). Chronic Ethanol Causes Persistent Increases in Alzheimer's Tau Pathology in Female 3xTg-AD Mice: A Potential Role for Lysosomal Impairment. Frontiers in behavioral neuroscience. https://doi.org/10.3389/fnbeh.2022.886634
Vancouver
Tucker AE, Alicea Pauneto CDM, Barnett AM, Coleman LG. Chronic Ethanol Causes Persistent Increases in Alzheimer's Tau Pathology in Female 3xTg-AD Mice: A Potential Role for Lysosomal Impairment. Frontiers in behavioral neuroscience. 2022. doi:10.3389/fnbeh.2022.886634. PMID: 35645744.
BibTeX
@article{tucker2022-35645744,
author = {Tucker, A. E. and Alicea Pauneto, C. D. M. and Barnett, A. M. and Coleman, L. G.},
title = {{Chronic Ethanol Causes Persistent Increases in Alzheimer's Tau Pathology in Female 3xTg-AD Mice: A Potential Role for Lysosomal Impairment}},
journal = {Frontiers in behavioral neuroscience},
year = {2022},
doi = {10.3389/fnbeh.2022.886634},
pmid = {35645744},
url = {https://doi.org/10.3389/fnbeh.2022.886634}
}
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Key findings
- Epidemiological studies have found that heavy alcohol use is associated with increased risk for Alzheimer's disease (AD), with frequent drinking earlier in adulthood increasing risk.
- Persistent AD pathology was associated with an increased proinflammatory signature and a reduction of mature lysosomes.
- This implicates binge ethanol exposure with increased risk of AD pathologic progression in females.
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Study details
- Evidence strengthLow
How this study scored 43/100
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. We have no data on journal's citation record, 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 25 of the 58 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in behavioral neuroscience) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 3 / 5 | 2022 — within 6 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 “3xtg”) — 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 | 2 / 2 | Indexed in PubMed (PMID 35645744) |
| Free to read | 2 / 2 | Free to read |
| Points | 25 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 25 of the 58 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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