amyloid-beta-peptides and HIV-Infections

In patients infected with the human immunodeficiency virus (HIV), the HIV-Tat protein may be continually produced despite adequate antiretroviral therapy. As the HIV-infected population is aging, it is becoming increasingly important to understand how HIV-Tat may interact with proteins such as amyloid β and Tau which accumulate in the aging brain and eventually result in Alzheimer's disease. In this review, we examine the in vivo data from HIV-infected patients and animal models and the in vitro experiments that show how protein complexes between HIV-Tat and amyloid β occur through novel protein-protein interactions and how HIV-Tat may influence the pathways for amyloid β production, degradation, phagocytosis, and transport. HIV-Tat may also induce Tau phosphorylation through a cascade of cellular processes that lead to the formation of neurofibrillary tangles, another hallmark of Alzheimer's disease. We also identify gaps in knowledge and future directions for research. Available evidence suggests that HIV-Tat may accelerate Alzheimer-like pathology in patients with HIV infection which cannot be impacted by current antiretroviral therapy.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Anti-HIV Agents; Brain Chemistry; Extracellular Space; HIV Infections; Humans; Low Density Lipoprotein Receptor-Related Protein-1; Lysosomes; Macrophages; Mice; Models, Molecular; Neprilysin; Neurofibrillary Tangles; Neuroglia; Peptide Fragments; Phagocytosis; Phosphorylation; Protein Binding; Protein Conformation; Protein Interaction Mapping; Protein Processing, Post-Translational; Protein Transport; Structure-Activity Relationship; tat Gene Products, Human Immunodeficiency Virus; tau Proteins

Imaging with β-amyloid (Aβ) positron emission tomography (PET) has the potential to aid the diagnosis of the cause of cognitive impairment affecting people living with HIV (PLWH) when neurodegenerative disorders are considered. We evaluated the clinical utility of [18F]Florbetaben (FBB) in PLWH with cognitive symptoms.. Imaging with FBB PET was performed in 20 patients with cognitive concerns about dementia. Neuropsychological testing, plasma neurofilament light protein, plasma Aβ40, Aβ42, and cerebrospinal fluid Aβ42, tau, and HIV RNA were obtained. FBB PET images were assessed visually by 3 readers blinded to the clinical diagnosis and quantitatively by obtaining a composite cortical to cerebellar cortex standardized uptake value ratio (SUVR). FBB SUVR from 10 age-matched healthy controls was compared with SUVR of PLWH.. Most participants were men (90%) of white ethnicity (90%) with a median age (interquartile range) of 59 (43-79) years. Median CD4 count was 682 (74-1056). All patients were on combination antiretroviral therapy with plasma and cerebrospinal fluid HIV RNA <40 copies/mL. Fourteen patients had objective cognitive impairment including 2 who met clinical criteria for a diagnosis of dementia. No significant differences in composite SUVRs between PLWH and controls [mean (SD): 1.18 (0.03) vs. 1.16 (0.09); P = 0.37] were observed. Four patients were FBB+ with the highest SUVR in the posterior cingulate, superior temporal, and frontal superior lobe. Amyloid PET results contributed to a change in diagnosis and treatment for 10 patients.. [18F]Florbetaben PET has potential as an adjunctive tool in the diagnosis of PLWH with cognitive impairment, increasing diagnostic certainty and optimizing management.

Topics: Adult; Aged; Amyloid beta-Peptides; Aniline Compounds; Brain; CD4 Lymphocyte Count; Cognitive Dysfunction; Drug Therapy, Combination; Female; HIV Infections; Humans; Male; Middle Aged; Neurodegenerative Diseases; Neuropsychological Tests; Peptide Fragments; Positron-Emission Tomography; RNA, Viral; Stilbenes; tau Proteins