UC San Diego
Increased Accumulation of Intraneuronal Amyloid β in HIV-Infected Patients
- Author(s): Achim, Cristian L.
- Adame, Anthony
- Dumaop, Wilmar
- Everall, Ian P.
- Masliah, Eliezer
- et al.
Published Web Locationhttps://doi.org/10.1007/s11481-009-9152-8
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 β (Aβ), which might participate in worsening the neurodegenerative process and cognitive impairment in older patients with HIV. For this purpose, levels and distribution of Aβ immunoreactivity were analyzed in the frontal cortex of 43 patients with HIV (ages 38–60) and HIV− age-matched controls. Subcellular localization of the Aβ-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 Aβ immunostaining in pyramidal neurons and along axonal tracts. Cases with HIV encephalitis (HIVE) had higher levels of intraneuronal Aβ immunoreactivity compared to HIV+ cases with no HIVE. Moreover, levels of intracellular Aβ correlated with age in the group with HIVE. Double-labeling analysis showed that the Aβ-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 Aβ 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 Aβ and worsen neuronal damage and cognitive impairment in this population.