Pathogenesis of age-related HIV neurodegeneration

被引:51
作者
Mackiewicz, Miroslaw [1 ]
Overk, Cassia [2 ]
Achim, Cristian L. [3 ]
Masliah, Eliezer [1 ,4 ]
机构
[1] NIA, Div Neurosci, NIH, Bethesda, MD 20892 USA
[2] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA
[3] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA
[4] NIA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA
关键词
Aging; Alzheimer's disease; HIV-associated cognitive impairment; Neurodegeneration; HUMAN-IMMUNODEFICIENCY-VIRUS; MULTIPLE SYSTEM ATROPHY; CENTRAL-NERVOUS-SYSTEM; NEUROCOGNITIVE DISORDERS; ALZHEIMERS-DISEASE; AMYLOID-BETA; ANTIRETROVIRAL THERAPY; PARKINSONS-DISEASE; NEURONAL INJURY; ALPHA-SYNUCLEIN;
D O I
10.1007/s13365-019-00728-z
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
People over the age of 50 are the fastest growing segment of the HIV-infected population in the USA. Although antiretroviral therapy has remarkable success controlling the systemic HIV infection, HIV-associated neurocognitive disorder (HAND) prevalence has increased or remained the same among this group, and cognitive deficits appear more severe in aged patients with HIV. The mechanisms of HAND in the aged population are not completely understood; a leading hypothesis is that aged individuals with HIV might be at higher risk of developing Alzheimer's disease (AD) or one of the AD-related dementias (ADRD). There are a number of mechanisms through which chronic HIV disease alone or in combination with antiretroviral therapy and other comorbidities (e.g., drug use, hepatitis C virus (HCV)) might be contributing to HAND in individuals over the age of 50 years, including (1) overlapping pathogenic mechanisms between HIV and aging (e.g., decreased proteostasis, DNA damage, chronic inflammation, epigenetics, vascular), which could lead to accelerated cellular aging and neurodegeneration and/or (2) by promoting pathways involved in AD/ADRD neuropathogenesis (e.g., triggering amyloid beta, Tau, or alpha-synuclein accumulation). In this manuscript, we will review some of the potential common mechanisms involved and evidence in favor and against a role of AD/ADRD in HAND.
引用
收藏
页码:622 / 633
页数:12
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