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Microglial Dysfunction and Amyloid-Beta Pathology in Alzheimer's Disease and HIV-Associated Neurocognitive Disorders
George Chigozie Njoku, Georgette Djuidje Kanmogne. International journal of molecular sciences, 2025-09-17
Topic: Inflammation, microglia and astrocytes
Chronic neuroinflammation and impaired protein clearance are hallmarks of neurodegenerative diseases such as Alzheimer's disease (AD) and HIV-associated neurocognitive disorders (HAND). Central to these processes are microglia, the brain's resident immune cells, which normally maintain brain homeostasis by clearing amyloid-beta (Aβ) and other misfolded proteins through phagocytosis and receptor-mediated degradation. However, in both AD and HAND, microglial dysfunction promotes ongoing inflammation, impaired Aβ clearance, and progressive neuronal damage. This review synthesizes evidence from human and animal studies showing how key microglial pattern recognition receptors, including the Triggering receptor expressed on myeloid cells 2 (TREM2), Toll-like receptors (TLRs), and scavenger receptors (SR-AI/II, CD36, SR-BI, CD163), coordinate Aβ sensing, uptake, and inflammatory responses. We describe how HIV infection and viral proteins such as the trans-activator of transcription (Tat) and glycoprotein 120 (gp120) disrupt these pathways by altering receptor expression, lysosomal function, and microglial metabolism, creating a cycle of neurotoxicity and amyloid buildup. We further highlight current scientific gaps in elucidating how HIV affects microglial function and implications for HAND.
Key findings
- Central to these processes are microglia, the brain's resident immune cells, which normally maintain brain homeostasis by clearing amyloid-beta (Aβ) and other misfolded proteins through phagocytosis and receptor-mediated degradation.
- However, in both AD and HAND, microglial dysfunction promotes ongoing inflammation, impaired Aβ clearance, and progressive neuronal damage.
- This review synthesizes evidence from human and animal studies showing how key microglial pattern recognition receptors, including the Triggering receptor expressed on myeloid cells 2 (TREM2), Toll-like receptors (TLRs), and scavenger receptors (SR-AI/II, CD36, SR-BI, CD163), coordinate Aβ sensing, uptake, and inflammatory responses.
- We describe how HIV infection and viral proteins such as the trans-activator of transcription (Tat) and glycoprotein 120 (gp120) disrupt these pathways by altering receptor expression, lysosomal function, and microglial metabolism, creating a cycle of neurotoxicity and amyloid buildup.
- We further highlight current scientific gaps in elucidating how HIV affects microglial function and implications for HAND.
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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, studied in people 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, multi-centre collaboration and free to read, so those were left out: it earned 24 of the 56 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (International journal of molecular sciences) |
| 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 | 4 / 5 | 2025 — within 3 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) |
| 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 41009633) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 24 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 24 of the 56 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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APA 7th
Njoku, G. C., & Kanmogne, G. D. (2025). Microglial Dysfunction and Amyloid-Beta Pathology in Alzheimer's Disease and HIV-Associated Neurocognitive Disorders. International journal of molecular sciences. https://doi.org/10.3390/ijms26189069
Vancouver
Njoku GC, Kanmogne GD. Microglial Dysfunction and Amyloid-Beta Pathology in Alzheimer's Disease and HIV-Associated Neurocognitive Disorders. International journal of molecular sciences. 2025. doi:10.3390/ijms26189069. PMID: 41009633.
BibTeX
@article{njoku2025-41009633,
author = {Njoku, George Chigozie and Kanmogne, Georgette Djuidje},
title = {{Microglial Dysfunction and Amyloid-Beta Pathology in Alzheimer's Disease and HIV-Associated Neurocognitive Disorders}},
journal = {International journal of molecular sciences},
year = {2025},
doi = {10.3390/ijms26189069},
pmid = {41009633},
url = {https://doi.org/10.3390/ijms26189069}
}
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