Dataset Information

An individual with human immunodeficiency virus, dementia, and central nervous system amyloid deposition.

ABSTRACT: Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) is found in 30%-50% of individuals with HIV infection. To date, no HIV+ individual has been reported to have a positive amyloid PET scan. We report a 71-year-old HIV+ individual with HAND. Clinical and neuropsychologic evaluations confirmed a progressive mild dementia. A routine brain MRI was normal for age. [18F]Fluorodeoxyglucose-PET revealed mild hypermetabolism in bilateral basal ganglia and hypometabolism of bilateral parietal cortex including the posterior cingulate/precuneus. Resting state functional MRI revealed altered connectivity as found with individuals with mild AD. CSF examination revealed a low A?42/tau index but a low phospho-tau. An amyloid PET/CT with [18F]florbetaben revealed pronounced cortical radiotracer deposition. This case report suggests that progressive dementia in older HIV+ individuals may be due to HAND, AD, or both. HIV infection does not preclude CNS A?/amyloid deposition. Amyloid PET imaging may be of value in distinguishing HAND from AD pathologies.

SUBMITTER: Turner RS

PROVIDER: S-EPMC4950581 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

An individual with human immunodeficiency virus, dementia, and central nervous system amyloid deposition.

Turner Raymond Scott RS Chadwick Melanie M Horton Wesley A WA Simon Gary L GL Jiang Xiong X Esposito Giuseppe G

Alzheimer's & dementia (Amsterdam, Netherlands) 20160415

Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) is found in 30%-50% of individuals with HIV infection. To date, no HIV+ individual has been reported to have a positive amyloid PET scan. We report a 71-year-old HIV+ individual with HAND. Clinical and neuropsychologic evaluations confirmed a progressive mild dementia. A routine brain MRI was normal for age. [18F]Fluorodeoxyglucose-PET revealed mild hypermetabolism in bilateral basal ganglia and hypometabolism of bilate ...[more]

PMID: 27489872

Similar Datasets

Project description:Infection of microglia and other cells of the macrophage/monocyte lineage in the central nervous system (CNS) by human immunodeficiency virus type I (HIV-1) underlies the development of giant cell encephalitis (GCE). It is currently unknown whether GCE depends on the emergence of virus populations specifically adapted to replicate in cells of the monocyte/macrophage lineage and whether this also leads to the specific targeting of macrophages in other nonlymphoid tissues. Autopsy samples from lymph node, brain (frontal region), lung, and full-thickness colon sections were obtained from nine study subjects with GCE and from nine without. The two groups showed no significant differences in CD4 counts, disease progression, or treatment history before death. Genetic relatedness between variants recovered from lymph node and nonlymphoid tissues was assessed by sequence comparison of V3 and p17(gag) regions using a newly developed method that scores the sample composition at successive nodes in a neighbor-joining tree. The association index enabled objective, numerical comparisons on the degree of tissue compartmentalization to be made. High proviral loads and p24 antigen expression in the brain were confined to the nine individuals with GCE. GCE was also associated with significantly higher proviral loads in colon samples (median of the GCE(+) group: 1,010 copies/10(6) cells; median of GCE(-) group, 10/10(6) cells; P = 0.006). In contrast, there were no significant differences in proviral load between the GCE(+) and GCE(-) groups in lymph node or lung samples, where HIV infection was manifested predominantly by infiltrates of lymphoid cells. V3 sequences from brain samples of individuals with GCE showed the greatest compartmentalization from those of lymph node, although samples from other tissues, particularly the colon, frequently contained variants phylogenetically related to those found in brain. The existence of shared, distinct populations of HIV specifically distributed in cells of the monocyte/macrophage lineage was further indicated by immunocytochemical detection of CD68(+), multinucleated giant cells expressing p24 antigen in samples of lung and colon in two individuals with GCE. This study provides the basis for future investigation of possible phenotypic similarities that underline the shared distributions of HIV variants infecting microglia and tissue macrophages outside the CNS.

Project description:BackgroundThe RNA-binding protein tristetraprolin (TTP) participates in normal post-transcriptional control of cytokine and chemokine gene expression, dysregulation of which contributes to the HIV-associated neurocognitive disorders. Transcriptional and post-transcriptional regulation of TTP has been described, including regulation by microRNA-29a. In the simian immunodeficiency virus (SIV) model of HIV CNS disease, control of cytokine/chemokine expression coincides with the end of acute phase infection. This control is lost during progression to disease. In this study, we assessed TTP regulation and association with cytokine regulation in the brain during SIV infection.ResultsQuantitation of TTP expression over the course of SIV infection revealed downregulation of TTP during acute infection, maintenance of relatively low levels during asymptomatic phase, and increased expression only during late-stage CNS disease, particularly in association with severe disease. The ability of miR-29a to regulate TTP was confirmed, and evidence for additional miRNA targeters of TTP was found. However, increased miR-29a expression in brain was not found to be significantly negatively correlated with TTP. Similarly, increased TTP during late-stage disease was not associated with lower cytokine expression.ConclusionsTTP expression is regulated during SIV infection of the CNS. The lack of significant negative correlation of miR-29a and TTP expression levels suggests that while miR-29a may contribute to TTP regulation, additional factors are involved. Reduced TTP expression during acute infection is consistent with increased cytokine production during this phase of infection, but the increases in TTP observed during late-stage infection were insufficient to halt runaway cytokine levels. While antisense inhibitors of the post-transcriptional targeters of TTP identified here could conceivably be used further to augment TTP regulation of cytokines, it is possible that high levels of TTP are undesirable. Additional research is needed to characterize members of the miRNA/TTP/cytokine regulatory network and identify nodes that may be best targeted therapeutically to ameliorate the effects of chronic inflammation in retrovirus-associated CNS disease.

Dataset Information

An individual with human immunodeficiency virus, dementia, and central nervous system amyloid deposition.

Publications

An individual with human immunodeficiency virus, dementia, and central nervous system amyloid deposition.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets