Year: 2009
Type: article
Study design: Observational Study
Abstract: 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.
Authors: HNRC, Cristian L. Achim, Anthony Adame, Wilmar Dumaop, Ian P. Everall, Eliezer Masliah
Institution: University of California San Diego
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,790
Awards: California NeuroAIDS Tissue Network (CNTN), Somatostain & Stress-Related Genes in HIV & Comorbid Major Depressive Disorder, PET Imaging of Amyloid in the HIV Brain, G3767897145, NEUROAIDS: EFFECTS OF METHAMPHETAMINE AND HCV, THERAPEUTIC TARGETS IN TRANSGENIC MICE, HIV NEUROBEHAVIORAL RESEARCH CENTER, G8570848313, Immunophilins in the neuroglial response to HIV infection, HIV Neurobehavioral Research Center
OpenAlex ID: W2162703492