HIV/neuroAIDS biomarkers

Abstract

HIV infection often causes neurological symptoms including cognitive and motor dysfunction, which have been collectively termed HIV/neuroAIDS. Neuropsychological assessment and clinical symptoms have been the primary diagnostic criteria for HIV/neuroAIDS, even for the mild cognitive and motor disorder, the most prevalent form of HIV/neuroAIDS in the era of combination antiretroviral therapy. Those performance-based assessments and symptoms are generally descriptive and do not have the sensitivity and specificity to monitor the diagnosis, progression, and treatment response of the disease when compared to objective and quantitative laboratory-based biological markers, or biomarkers. In addition, effects of demographics and comorbidities such as substance abuse, psychiatric disease, nutritional deficiencies, and co-infection on HIV/neuroAIDS could be more readily determined using biomarkers than using neuropsychological assessment and clinical symptoms. Thus, there have been great efforts in identification of HIV/neuroAIDS biomarkers over the past two decades. The need for reliable biomarkers of HIV/neuroAIDS is expected to increase as the HIV-infected population ages and their vulnerability to neurodegenerative diseases, particularly Alzheimer’s disease increases. Currently, three classes of HIV/neuroAIDS biomarkers are being pursued to establish objective laboratory-based definitions of HIV-associated neurologic injury: cerebrospinal fluid biomarkers, blood biomarkers, and neuroimaging biomarkers. In this review, we will focus on the current knowledge in the field of HIV/neuroAIDS biomarker discovery.

Differentiating HIV-Associated Neurocognitive Disorders From Alzheimer’s Disease: an Emerging Issue in Geriatric NeuroHIV

“…[32] HIV protein gp120 promotes amyloid aggregation by triggering a pathological cascade resulting in axonal injury or inducing microglial activation, altering transcription and cleavage of amyloid precursor protein (APP). [31, 33, 34] Alterations of APP cleavage products have also been described in HAD patients. [35, 36] The protein tat has been shown to promote amyloid accumulation by inhibiting neprilysin, a proteolytic enzyme that prevents amyloid accumulation, or altering endolysosome structure and function.…”

“…[35, 36] The protein tat has been shown to promote amyloid accumulation by inhibiting neprilysin, a proteolytic enzyme that prevents amyloid accumulation, or altering endolysosome structure and function. [31, 34, 37, 38]…”

“…Current reports note low or normal levels of amyloid, while t-tau and p-tau have been shown to be alternately elevated or reduced. [29, 34, 35, 67-69] One study documented lower CSF amyloid levels in cognitively impaired HIV-infected participants and individuals with mild AD, but not in cognitively normal HIV-infected subjects. [29] They also found that the characteristically elevated CSF tau seen in AD was absent in HAND, leading some to conclude that the common decrease in CSF amyloid compared to unimpaired HIV-infected individuals and AD patients in concert with increased tau levels in AD but not in HAND provides hope for diagnostic clarity between AD and HAND.…”

“…[34] Some reports indicated NFL as the most sensitive biomarker in detecting neuronal injury compared to biomarkers such as soluble APPs or t-tau, suggesting the presence of CNS axonal damage in HAD individuals, but also in those patients with decreased CD4 cell count. [35, 70] Treatment-induced viral suppression was instead associated with normal or slightly elevated CSF NFL levels.…”

Astroglial connexins and cognition: memory formation or deterioration?

“…The development of HIV-Associated Neurocognitive Disorders (HANDs) is one of the major complications of AIDS and cognitive impairment is found in approximately 50-60% of HIV-infected patients [69,70]. It has been shown that HIV-associated deleterious effects in the brain, particularly the neuronal loss is mediated through an increase in connexin 43 expression [71].…”