Increased Accumulation of Intraneuronal Amyloid β in HIV-Infected Patients
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In recent years, human immunodeficiency virus (HIV)-infected patients under highly active anti-retroviral therapy (HAART) regimens have shown a markedly improved general clinical status; however, the prevalence of mild cognitive disorders has increased. We propose that increased longevity with HIV-mediated chronic inflammation combined with the secondary effects of HAART may increase the risk of early brain aging as shown by intraneuronal accumulation of abnormal protein aggregates like amyloid beta (Abeta), which might participate in worsening the neurodegenerative process and cognitive impairment in older patients with HIV. For this purpose, levels and distribution of Abeta immunoreactivity were analyzed in the frontal cortex of 43 patients with HIV (ages 38-60) and HIV- age-matched controls. Subcellular localization of the Abeta-immunoreactive material was analyzed by double labeling and confocal microscopy and by immunono-electron microscopy (EM). Compared to HIV- cases, in HIV+ cases, there was abundant intracellular Abeta immunostaining in pyramidal neurons and along axonal tracts. Cases with HIV encephalitis (HIVE) had higher levels of intraneuronal Abeta immunoreactivity compared to HIV+ cases with no HIVE. Moreover, levels of intracellular Abeta correlated with age in the group with HIVE. Double-labeling analysis showed that the Abeta-immunoreactive granules in the neurons co-localized with lysosomal markers such as cathepsin-D and LC3. Ultrastructural analysis by immuno-EM has confirmed that in these cases, intracellular Abeta was often found in structures displaying morphology similar to autophagosomes. These findings suggest that long-term survival with HIV might interfere with clearance of proteins such as Abeta and worsen neuronal damage and cognitive impairment in this population.
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Brains from post-mortem HIV patients display increased levels of deposited Aβ and hyperphosphorylated tau compared to age-matched controls.
“Moreover, brains from post‐mortem HIV patients display increased levels of deposited amyloid beta (Aβ) and hyperphosphorylated tau compared to age‐matched controls, suggesting pathological links exist between Alzheimer’s disease and HAD (Green et al, 2005; Anthony et al, 2006; Achim et al, 2009).”
From The struggle of a good friend getting old: cellular senescence in viral responses and therapy (2021) · cites this paper as Achim et al, 2009
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Self-citation
- Authors
- HNRC, Achim, C. L., Adame, A., Dumaop, W., Everall, I. P., & Masliah, E.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Masliah, Eliezer
- Venue
- Journal of Neuroimmune Pharmacology
- Published
- 2009-03-17
- Volume
- 4
- Issue
- 2
- Pages
- 190-199
- ISSN
- 1557-1890 (ISSN-L)
- 1557-1904
- PMC
- PMC3055557
- OpenAlex
- W2162703492
- Cited by
- 205
- References
- 88
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 5 · 2023: 4 · 2022: 15 · 2021: 11 · 2020: 19 · 2019: 18 · 2018: 13 · 2017: 16 · 2016: 11 · 2015: 7 · 2014: 20 · 2013: 11 · 2012: 8
- FWCI
- 7.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Journal of Neuroimmune Pharmacology (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (5r01mh058164-03)
- National Institute of Mental Health (U01-MH83506, U01MH083506, R01MH079881, R21MH072529, MH79881, MH-62512, MH5974, P50MH045294, MH076681, MH58164, R21MH076681, P30MH062512)
- National Institute on Drug Abuse (DA12065, P01DA012065)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- intraneuronal amyloid-beta, HIV infection, HIV-associated neurocognitive disorders, HIV encephalitis, autophagy, autophagosomes, lysosomes, cathepsin D, LC3, frontal cortex, pyramidal neurons, neurodegeneration, brain aging, chronic inflammation, highly active antiretroviral therapy, cognitive impairment
- MeSH terms
- Adult, Brain, Cathepsin D, Inclusion Bodies, Encephalitis, Female, Humans, Image Interpretation, Computer-Assisted, Immunohistochemistry, Lysosomes, Male, Microtubule-Associated Proteins, Middle Aged, Neurons, HIV Infections, Amyloid beta-Peptides, Microscopy, Immunoelectron, Microscopy, Confocal, Lysosomal Membrane Proteins, Lysosomal-Associated Membrane Protein 2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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