Increased accumulation of intraneuronal amyloid beta in HIV-infected patients
Cristian L Achim, Anthony Adame, Wilmar Dumaop, Ian P Everall, Eliezer Masliah, Neurobehavioral Research Center, Igor Grant, J Hampton Atkinson, Ronald J Ellis, J Allen McCutchan, Thomas D Marcotte, Melanie Sherman, Braden R Hale, Ronald J Ellis, J Allen McCutchan, Scott Letendre, Edmund Capparelli, Rachel Schrier, Jennifer Marquie-Beck, Terry Alexander, Janis Durelle, Robert K Heaton, Mariana Cherner, Steven Paul Woods, David J Moore, Matthew Dawson, Terry Jernigan, Christine Fennema-Notestine, Sarah L Archibald, John Hesselink, Jacopo Annese, Michael J Taylor, Brian Schweinsburg, Eliezer Masliah, Ian P Everall, Cristian L Achim, Douglas Richman, David M Smith, J Allen McCutchan, Ian P Everall, Stuart Lipton, J Allen McCutchan, J Hampton Atkinson, Ronald J Ellis, Scott Letendre, J Hampton Atkinson, Rodney von Jaeger, Anthony C Gamst, Clint Cushman, Daniel R Masys, Ian Abramson, Florin Vaida, Christopher Ake, Cristian L Achim, Anthony Adame, Wilmar Dumaop, Ian P Everall, Eliezer Masliah, Neurobehavioral Research Center, Igor Grant, J Hampton Atkinson, Ronald J Ellis, J Allen McCutchan, Thomas D Marcotte, Melanie Sherman, Braden R Hale, Ronald J Ellis, J Allen McCutchan, Scott Letendre, Edmund Capparelli, Rachel Schrier, Jennifer Marquie-Beck, Terry Alexander, Janis Durelle, Robert K Heaton, Mariana Cherner, Steven Paul Woods, David J Moore, Matthew Dawson, Terry Jernigan, Christine Fennema-Notestine, Sarah L Archibald, John Hesselink, Jacopo Annese, Michael J Taylor, Brian Schweinsburg, Eliezer Masliah, Ian P Everall, Cristian L Achim, Douglas Richman, David M Smith, J Allen McCutchan, Ian P Everall, Stuart Lipton, J Allen McCutchan, J Hampton Atkinson, Ronald J Ellis, Scott Letendre, J Hampton Atkinson, Rodney von Jaeger, Anthony C Gamst, Clint Cushman, Daniel R Masys, Ian Abramson, Florin Vaida, Christopher Ake
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.
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Source: PubMed