Table 1.
Common neurotoxicity pathways between Alzheimer’s disease (AD) and human immunodeficiency virus (HIV).
| AD symptoms | Observation in HIV+ patients | Observations in in vivo and in vitro HIV models |
|---|---|---|
| Misprocessing of APP and Aβ synthesis | Increase in CSF Aβ1–42 (ELISA; Brew et al., 2005) Presence of amyloid plaques in brain (Esiri et al., 1998; Green et al., 2005) | Increase of amyloid plaques production (Congo red staining; Cho et al., 2017) Increase of C99 fragment (western blot; Cho et al., 2017) Increase of Aβ1–42 (ELISA; Kim et al., 2013) |
| Abnormal Tau phosphorylation | Increase in CSF total and phosphorylated Tau (ELISA; Brew et al., 2005; Anthony et al., 2006) Increase of GSK3β, Cdk5 and p35 in frontal cortex (Patrick et al., 2011) | Increase of p-Thr181, p-Thr231, p-Ser396, p-Ser404 (western blot; Kang et al., 2010; Cho et al., 2017) Increase of Cdk5 and GSK3β contents (western blot; Kang et al., 2010; Cho et al., 2017) |
| Activation of death pathways and apoptosis | Increase of apoptosis (TUNEL; Lannuzel et al., 1997) Increase of JNK/ERK contents and activities (western blot and kinases assay; Lannuzel et al., 1997) | Increase of caspase 3, Bax, pJNK/JNK, Erk contents (western blot; Kruman et al., 1998; Kaul and Lipton, 1999; Cho et al., 2017) Increase of apoptosis (TUNEL; Kruman et al., 1998) |
| Oxidative Stress | Oxidative stress, ROS production, mitochondrial dysfunction, impaired glucose metabolism (Vignoli et al., 2000) | Increase of NAPDH oxydase, CYP2E1, iNOS, IkB, HIF-1 (western blot; Cho et al., 2017) |
| Neuroinflammation | Massive gliosis through peripheral macrophages invasion and chemokines release (Peters et al., 2004) | Increase of astrocytes GFAP and microglial Iba1 (western blot and histology; Kang et al., 2010; Cho et al., 2017) Increase of proinflammatory cytokines (TNF, IL6, MCP-1; western blot; Cho et al., 2017) |
| Excitotoxicity | Increased CSF glutamate levels (ELISA; Ferrarese et al., 2001) | Increase glutamate release and decrease glutamate reuptake by astrocytes (Dreyer and Lipton, 1995; Belmadani et al., 2001) |
| Neurodegeneration | Cortical gray and white matter loss (post mortem histological study; Masliah et al., 1992) About 20%–50% neuronal loss in the frontal cortex (Ketzler et al., 1990) | Decrease of NeuN (western blot; Kang et al., 2010; Cho et al., 2017) Impaired neurogenesis (Mishra et al., 2010) |
| Cognitive and learning deficits | Decrease of memory performances (Becker et al., 2009) | Learning deficits (Morris Water Maze; Vigorito et al., 2007) |
| Blood Brain Barrier | Increased CSF/plasma albumin ratio in HAD patients (Anesten et al., 2016) | HIV infection increases leukocytes transmigration through tight junctions (TJs) proteins down regulation and metalloproteinases upregulation (Eugenin et al., 2011) |
| HPA axis deregulation | Glucocorticoid resistance, modification of glucocorticoid sensitivity, altered cytokine production (Chrousos and Zapanti, 2014) Adrenal insufficiency, elevated plasma GC (Christeff et al., 1997; Kino, 2000) | Increase of hypothalamic CRF levels, AVP levels and CRF mRNA levels (Costa et al., 2000) |