Aids Dementia
Introduction
Section titled “Introduction”AIDS dementia, also known as HIV-associated dementia (HAD) or HIV-associated neurocognitive disorder (HAND), refers to a range of neurological complications observed in individuals infected with Human Immunodeficiency Virus (HIV). This condition encompasses a spectrum of cognitive impairments, from subtle neurocognitive impairment (NCI) to severe dementia, affecting various cognitive domains.[1] Historically, before the widespread availability of effective antiretroviral therapy (ART), HAD was a prevalent and debilitating condition among people living with HIV. While the incidence of severe HAD has declined significantly with modern ART, milder forms of neurocognitive impairment remain a significant clinical concern, impacting the daily lives of many HIV-infected individuals.
Biological Basis
Section titled “Biological Basis”The biological underpinnings of AIDS dementia involve the complex interplay between HIV infection and the central nervous system (CNS). HIV can directly and indirectly affect brain cells, particularly macrophages and microglia, leading to chronic inflammation, oxidative stress, and neuronal damage, even without direct infection of neurons. These processes can disrupt synaptic function and neuronal networks, contributing to cognitive decline. Genetic factors are increasingly recognized for their role in modulating susceptibility and progression of neurocognitive impairment in HIV-infected adults. Genome-wide association studies (GWAS) are employed to identify specific genetic variants, such as single nucleotide polymorphisms (SNPs), that may be associated with the prevalence of HAD or NCI, or influence the rate of neurocognitive decline.[1]Identifying these genetic markers can shed light on the underlying disease mechanisms and potential therapeutic targets.
Clinical Relevance
Section titled “Clinical Relevance”Clinically, AIDS dementia typically manifests as impairments in memory, attention, executive function, and psychomotor speed. These cognitive deficits can severely compromise an individual’s ability to perform daily activities, maintain employment, and adhere to their prescribed HIV treatment regimens, thereby affecting their overall quality of life. Early identification and management of neurocognitive impairments are critical for optimizing patient outcomes. Understanding the genetic predispositions to AIDS dementia can facilitate early risk stratification, enable more personalized therapeutic strategies, and guide the development of targeted interventions to mitigate cognitive decline.
Social Importance
Section titled “Social Importance”The social impact of AIDS dementia is substantial, extending beyond the individual to their families, caregivers, and healthcare systems. Cognitive impairments can lead to loss of independence, social isolation, and increased healthcare utilization. As the population of individuals living with HIV ages due to the effectiveness of ART, the burden of chronic comorbidities, including neurocognitive disorders, becomes more prominent. Research into the genetic architecture of AIDS dementia is vital for improving long-term health outcomes, reducing health disparities, and enhancing the quality of life for the aging HIV-infected population, underscoring its significant public health importance.
Limitations
Section titled “Limitations”Methodological and Statistical Constraints
Section titled “Methodological and Statistical Constraints”The studies on dementia genetics are subject to various methodological and statistical limitations that influence the scope and certainty of their findings. While some investigations leverage large cohorts like the UK Biobank, providing substantial statistical power for common variants . This gene’s impact on neuroinflammation and neuronal repair mechanisms may also contribute to the neuropathological changes observed in HIV-associated neurocognitive disorders (HAND). Similarly, variants nearNECTIN2 and BCAM, such as rs6857 and rs10402524 , are implicated in cellular adhesion and immune responses. NECTIN2encodes a protein involved in cell-cell adhesion and is a known entry receptor for certain viruses, including herpes simplex virus, suggesting that variations could modulate viral entry or immune cell trafficking in the context of HIV infection, thereby impacting neuroinflammation and dementia risk.
The BIN1 gene, represented by variants like rs4663105 , rs744373 , and rs730482 , is another significant genetic locus associated with Alzheimer’s pathology, and its role as a microglial activator and in endocytosis pathways is critical for synaptic function and waste clearance in the brain. Dysregulation of BIN1can lead to impaired endosomal trafficking and increased neuroinflammation, mechanisms that are also central to the progression of AIDS dementia.[2] Similarly, variants in the MS4A6A gene, such as rs12453 and rs2278867 , are known to influence microglial function and immune responses in the central nervous system. As part of the MS4A gene cluster, MS4A6Ais linked to immune cell activation and has been associated with late-onset Alzheimer’s disease, suggesting its variants could modulate the neuroinflammatory environment in AIDS dementia.[3] Altered microglial activity is a hallmark of HAND, making these genetic influences particularly relevant.
Other genetic variants also contribute to the complex landscape of dementia susceptibility. TheHCP5 gene, with variant rs2395029 , is located in the major histocompatibility complex (MHC) region, a critical area for immune system function and viral control. Variations in HCP5have been linked to HIV disease progression, and its role in immune regulation could influence the chronic inflammation and immune activation seen in AIDS dementia. Long non-coding RNAs, such as those associated withMIATNB and MIAT (rs563910796 ), can regulate gene expression and cellular processes critical for neuronal health and survival. Dysregulation of these non-coding RNAs could contribute to neurodegeneration by influencing stress responses or inflammatory pathways. Furthermore, variants like rs556399519 in FGGY, rs146791569 near OLFM1 and LINC02907, and rs36113352 near NRP1 and LINC02628may impact diverse cellular functions ranging from protein glycosylation and neuronal development to cell signaling and vascular integrity. These genes, though less directly studied in the context of AIDS dementia, represent potential pathways through which genetic variations could modulate the brain’s resilience to chronic inflammation, oxidative stress, and neurotoxic effects associated with HIV infection.
Classification, Definition, and Terminology
Section titled “Classification, Definition, and Terminology”Defining HIV-Associated Neurocognitive Disorders (HAND)
Section titled “Defining HIV-Associated Neurocognitive Disorders (HAND)”The condition commonly referred to as ‘aids dementia’ is more precisely understood within the spectrum of HIV-Associated Neurocognitive Disorders (HAND). This encompasses a range of cognitive impairments occurring in individuals infected with HIV, with varying degrees of severity. A specific and severe manifestation within this spectrum is HIV-Associated Dementia (HAD), which is clinically diagnosed in HIV-positive participants.[1]Another related classification, neurocognitive impairment (NCI), refers to a broader state where HIV-positive individuals are coded as either “ever impaired” or “never impaired,” indicating a decline in cognitive function.[1]These precise definitions allow for the study of prevalence and progression, distinguishing these conditions from other forms of dementia.
Diagnostic and Classification Frameworks for Neurocognitive Impairment
Section titled “Diagnostic and Classification Frameworks for Neurocognitive Impairment”The classification of neurocognitive impairment, including HAD and NCI, often relies on established diagnostic frameworks that categorize the severity and type of cognitive decline. Standardized systems such as the International Classification of Diseases (ICD-10 codes, e.g., F00, F01, F02, F03, G30) are used for clinically diagnosing dementia from health records and death registers.[4]Similarly, the Structured Interview for Diagnosis of Dementia of Alzheimer type, Multi-Infarct Dementia and Dementia of other etiology (SIDAM) employs both DSM-IV and ICD-10 criteria for diagnosis.[5]These systems also allow for distinctions between stages of cognitive decline, such as Cognitively Normal (CN), Mild Cognitive Impairment (MCI), and overt dementia, as observed in studies of Alzheimer’s disease.[6] Approaches to assessment can be categorical, modeling binary outcomes like the presence or absence of HAD or NCI, or dimensional, utilizing continuous measures such as the rate of neurocognitive decline [1]. [7]
Measurement Approaches and Biomarkers in Dementia Assessment
Section titled “Measurement Approaches and Biomarkers in Dementia Assessment”Diagnosis and classification of neurocognitive disorders, including HIV-associated forms, are supported by a variety of clinical and research measurement approaches. Neuropsychological test batteries, such as the Mini-Mental State Examination (MMSE), the Clinical Dementia Rating - Sum of Boxes (CDR-SB), the Functional Activities Questionnaire (FAQ), and the Alzheimer’s Disease Assessment Scale 13-item Cognitive Subscale (ADAS13), are routinely employed to assess cognitive domains like memory, orientation, and intellectual abilities[5], [8]. [7] Beyond cognitive assessments, biomarkers from cerebrospinal fluid (CSF), such as amyloid-beta 1–42 (Aβ1–42) and phosphorylated tau (pTau), provide insights into underlying pathology [5]. [8]Furthermore, neuroimaging techniques, including amyloid and tau PET scans or volumetric measurements of brain regions like the fusiform and entorhinal cortices, help depict the extent of cognitive impairment and dementia-related changes[7]. [2] Post-mortem neuropathological assessments, which include staging systems like the Braak stage for neurofibrillary tangles and the Thal phases for amyloid-beta deposition, offer definitive classification of pathological changes [2], [9]. [10]
Signs and Symptoms of AIDS Dementia
Section titled “Signs and Symptoms of AIDS Dementia”Neurocognitive Decline and Symptom Manifestation
Section titled “Neurocognitive Decline and Symptom Manifestation”HIV-infected adults may present with neurocognitive decline, which can manifest as new neurologic symptoms or a measurable deterioration in cognitive function.[1]This decline can affect specific cognitive domains, such as processing speed (referred to as SPEED) and executive function (referred to as EXEC).[1]The severity and progression of neurocognitive impairment are heterogeneous and can be influenced by various clinical factors, including the presence of depression, the specifics of antiretroviral therapy, history of alcohol and drug use, nadir CD4 cell count, and co-infection with Hepatitis C.[1]
The detection of new neurologic symptoms reported by participants or objective evidence of neurocognitive decline identified through testing are significant indicators. [1]These findings typically prompt a referral for a comprehensive neurological examination by a study neurologist, which is critical for further diagnostic evaluation and to characterize the clinical phenotype of HIV-associated dementia (HAD) or neurocognitive impairment (NCI).[1] Such systematic referrals and examinations contribute to understanding the spectrum of clinical presentations and their diagnostic significance in this population.
Assessment and Monitoring of Cognitive Impairment
Section titled “Assessment and Monitoring of Cognitive Impairment”The assessment of neurocognitive impairment in HIV-infected adults relies on a combination of objective and subjective measures. [1] Objective evaluation primarily involves neuropsychological testing, which quantifies cognitive performance across various domains. [1] Complementing this, subjective reports of new medical conditions or neurologic symptoms by participants during regular visits are also systematically recorded and contribute to the initial detection of potential decline. [1]
To track and quantify the rate of neurocognitive decline, especially in domains like SPEED and EXEC, researchers utilize linear mixed models (LMM). [1]These models generate participant-specific slopes that estimate individual changes in cognitive function over time, accounting for confounding variables such as time since first visit, depression severity, antiretroviral therapy, alcohol and drug use, nadir CD4 cell count, and Hepatitis C infection.[1]These derived participant-specific slopes serve as a valuable continuous phenotype for genetic association analyses and help characterize the trajectory and severity of cognitive impairment, informing both diagnostic and prognostic indicators.[1]
Causes
Section titled “Causes”Genetic Predisposition
Section titled “Genetic Predisposition”Genetic factors play a significant role in determining susceptibility to neurocognitive impairment and dementia, including in HIV-infected individuals. Genome-wide association studies (GWAS) have identified numerous genetic variants and specific genes associated with various forms of dementia, indicating a complex polygenic risk architecture.[1] For instance, the APOEgene is consistently highlighted as a major susceptibility factor, with its ε4 allele strongly associated with both all-cause dementia and vascular dementia, exhibiting a substantial effect size such as an odds ratio of 2.90 forAPOE ε4/ε4 carriers compared to ε3 homozygotes. [3] Beyond APOE, other genes like ABCA7, TREM2, CR1, MS4A6A, ACE, and APOC4have been identified as functional genes within loci exhibiting genome-wide association with dementia, with some variants inABCA7 and TREM2 being candidate causal variants. [3]Mendelian forms of dementia are also recognized, exemplified by strong causative mutations such asPSEN1 E280A, which underscores the importance of investigating genetic associations even in the presence of highly penetrant variants. [11]
Epigenetic and Regulatory Mechanisms
Section titled “Epigenetic and Regulatory Mechanisms”Beyond direct genetic sequence variations, epigenetic and gene regulatory mechanisms contribute to the development of dementia. Functional enrichment analyses leverage GWAS data to identify regulatory annotations, including histone modifications, transcription factor binding sites, chromatin segmentation states, and open chromatin data, which characterize traits of interest.[12]Regulome-wide association analyses (RWAS) further pinpoint candidate enhancers that may mediate disease risk by altering the regulation of nearby gene expression, highlighting the dynamic interplay between genetic loci and their regulatory landscape.[13]The observed associations often involve gene expression quantitative trait loci (eQTLs) that colocalize with regulatory marks like enhancer and promoter binding sites, regulating the expression of specific genes in disease-relevant tissues.[3]This indicates that changes in gene expression, influenced by these epigenetic and regulatory elements, are critical mechanisms underlying dementia pathogenesis.
Interacting Factors and Comorbidities
Section titled “Interacting Factors and Comorbidities”The development of dementia is often influenced by a complex interplay of genetic predispositions, environmental factors, and co-occurring health conditions. While specific gene-environment interactions for AIDS dementia are not extensively detailed, research on general dementia highlights that modifiable risk factors, such as hypertension, are critical for population-level prevention, suggesting that environmental influences can interact with genetic vulnerabilities.[3]Furthermore, age is a consistently acknowledged factor, often adjusted for in genetic analyses, indicating its pervasive impact on dementia risk.[1]Various comorbidities and co-incident neuropathological features are also implicated; for example, Lewy body dementia (LBD) has shown nominal associations withMEF2C and SORL1, and vascular brain injury (VBI) withNME8, demonstrating how different neurological conditions can share or contribute to the genetic etiology of dementia.[9]
Biological Background
Section titled “Biological Background”Dementia, including forms observed in HIV-infected individuals, is a complex neurodegenerative condition characterized by a decline in cognitive function that interferes with daily life. The underlying biological mechanisms involve a multifaceted interplay of genetic predispositions, cellular dysfunctions, neuropathological changes, and systemic factors like inflammation and vascular health.[1]Research into various forms of dementia, such as Alzheimer’s disease and related dementias (ADRD), all-cause dementia (ACD), and vascular dementia (VaD), reveals common and distinct biological pathways contributing to cognitive decline.[4]
Genetic Susceptibility and Epigenetic Regulation
Section titled “Genetic Susceptibility and Epigenetic Regulation”Genetic factors play a significant role in determining an individual’s susceptibility to dementia. TheAPOEε4allele is a well-established strong genetic risk factor for Alzheimer’s disease and is also associated with all-cause and vascular dementia.[4] Beyond APOE, genome-wide association studies (GWAS) and whole exome sequencing (WES) have identified other critical genes such as TREM2 and ABCA7, with variants like a TREM2 stop mutation and specific non-synonymous ABCA7 variants (rs73505232 , rs59851484 ) linked to dementia risk.[14]These genetic associations often involve single nucleotide polymorphisms (SNPs) that can act as expression quantitative trait loci (eQTLs), influencing the expression levels of nearby or distant genes in disease-relevant tissues.[3]
Regulatory mechanisms, including epigenetic modifications, further modulate gene expression and contribute to dementia pathophysiology. Genes likeDNMT3L(DNA methyltransferase-3-like) encode factors that can promote or inhibit DNA methylation, a process shown to influence cognitive decline and exhibit differential hydroxymethylated regions in Alzheimer’s disease brains.[4] Similarly, MORC1(Microchidia family CW-type zinc finger 1), essential for de novo DNA methylation and silencing of transposable elements, has methylation patterns associated with microstructural features of the hippocampus and medial prefrontal cortex, suggesting its involvement in neurobiological processes related to neuropsychiatric disorders.[4] Differential gene expression, where genes such as EML6, CDA, SH2D5, and GOPCare found to be up or downregulated in brain tissue from individuals with dementia, highlights the dynamic nature of gene regulation in disease progression.[14]
Cellular and Molecular Dysfunctions in Neurodegeneration
Section titled “Cellular and Molecular Dysfunctions in Neurodegeneration”At the cellular and molecular level, dementia pathogenesis involves disruptions in critical cellular functions and the aberrant behavior of key biomolecules. Proteins likeTGM2 (Transglutaminase 2), a multifunctional acyltransferase, catalyze calcium-dependent post-translational modifications that can induce protein cross-linking, a process potentially contributing to the accumulation of abnormal protein aggregates characteristic of neurodegenerative diseases. [4] Oxidative stress is another significant contributor, with genes such as MSRA(Methionine Sulfoxide Reductase A) playing a role in reducing harmful reactive oxygen species like methionine sulfoxide, which are prevalent during inflammatory responses.[14] Dysregulation of MSRA or its associated pathways can therefore exacerbate cellular damage.
Furthermore, neuronal processes critical for healthy brain function are often compromised. Modules of genes enriched in dementia studies are involved in ‘chemical synaptic transmission’, ‘dendrite’ morphology, and ‘axon guidance’, indicating widespread neuronal dysfunction.[6] Microtubule dynamics, essential for neuronal structure and transport, are also affected, with genes like EML6 potentially modifying microtubule assembly to make them longer and more dynamic. [6]The formation of amyloid-beta plaques and neurofibrillary tangles composed of phosphorylated tau are central to Alzheimer’s disease pathology, with genes likeAPP and MAPT being key players in these processes. [6] SUCLG2has been identified as a determinator of cerebrospinal fluid Aβ1-42 levels and an attenuator of cognitive decline.[5]
Neuropathological Hallmarks and Brain Region Specificity
Section titled “Neuropathological Hallmarks and Brain Region Specificity”The macroscopic and microscopic alterations in the brain are fundamental to the clinical manifestation of dementia. Clinico-pathologic Alzheimer’s disease dementia is characterized by core neuropathologic changes, including neurofibrillary tangles (NFT Braak stage) and neuritic plaque (NP) scores, which reflect the extent of protein aggregation and neuronal damage.[9]Beyond these classical hallmarks, other neuropathologies such as microinfarcts, lacunar or territorial infarcts, and hippocampal sclerosis also contribute to the complex spectrum of dementia.[9]
Specific brain regions exhibit differential vulnerability and pathological changes in dementia. Expression profiling data have shown that specific expression levels of dementia-related genes differ in the entorhinal cortex, hippocampus, temporal cortex, and frontal cortex between individuals with and without Alzheimer’s disease.[4] The prefrontal cortex, for instance, shows significant downregulation of genes like EML6in Alzheimer’s disease brains, and RNA sequencing data from the dorsolateral prefrontal cortex have been crucial in examining gene expression in relation to Alzheimer’s pathologies.[10]Functional analyses reveal enrichment of genes associated with dementia endophenotypes in processes like synapse plasticity, axon quantity, microtubule dynamics, abnormal morphology of the dentate gyrus, and neuronal development, highlighting the profound impact of the disease on neuronal architecture and function.[6]
Neuroinflammation and Vascular Contributions to Dementia
Section titled “Neuroinflammation and Vascular Contributions to Dementia”Systemic and central nervous system inflammation, alongside vascular abnormalities, are increasingly recognized as critical drivers in the development and progression of dementia. Genes involved in immune responses and inflammation, such asCDA(Cytidine Deaminase), which is a marker of monocyte to macrophage differentiation, indicate the active involvement of immune cells in brain pathology.[14] The MSRAgene, through its role in reducing reactive oxygen species during neutrophil- and macrophage-mediated responses to bacterial infection, further links immune function and oxidative stress to dementia risk.[14]
Vascular dementia (VaD) and vascular contributions to all-cause dementia are significant. Variants nearHBEGF (Heparin Binding EGF like growth factor) are implicated in the pathobiology of cerebral autosomal dominant arteriopathy with sub-cortical infarcts and leukoencephalopathy (CADASIL), a Mendelian prototype of VaD. [3] HBEGF also affects angiogenesis, the expression of vascular endothelial growth factor A (VEGF-A), inflammation, and oxidative stress, underscoring the interconnectedness of vascular health, inflammation, and cellular stress in dementia.[3] Other genes like CR1 and MS4A6Ahave also been identified in loci associated with all-cause and vascular dementia, suggesting their roles in immune regulation, complement activation, or other vascular processes that contribute to cognitive decline.[3]
Ethical or Social Considerations
Section titled “Ethical or Social Considerations”Ethical Frameworks for Genetic Information
Section titled “Ethical Frameworks for Genetic Information”The application of genetic research to conditions like AIDS dementia introduces complex ethical considerations, particularly concerning informed consent, privacy, and the potential for discrimination. Given that individuals with HIV may constitute a vulnerable population, ensuring truly informed consent for genetic testing is paramount. This often requires careful consideration, especially for those who may already experience neurocognitive impairment, necessitating consent from caregivers, legal guardians, or other proxies.[1] The highly sensitive nature of both HIV status and genetic information demands robust privacy protections to prevent unauthorized access or misuse of data. Debates surrounding genetic testing also encompass reproductive choices, as identifying genetic predispositions could influence decisions about family planning, adding another layer of complexity to personal autonomy.
Furthermore, the potential for genetic discrimination in areas such as employment, insurance, or social services presents a significant ethical challenge. If genetic markers for AIDS dementia are identified, individuals carrying these markers could face unwarranted prejudice, exacerbating existing societal biases against people with HIV. Safeguarding individuals from such discrimination requires proactive measures and clear ethical guidelines for how genetic information can and cannot be used. The balance between advancing scientific understanding and protecting individual rights and well-being remains a central ethical dilemma in this field.
Social Stigma and Health Disparities
Section titled “Social Stigma and Health Disparities”The identification of genetic predispositions to AIDS dementia carries substantial social implications, particularly the potential to intensify the stigma already associated with HIV. For individuals identified with such genetic markers, this could lead to increased social isolation, psychological distress, and further marginalization within their communities. These findings also intersect with existing health disparities, where access to advanced genetic testing and subsequent specialized care for AIDS dementia is often unevenly distributed. Socioeconomic factors, including poverty, lack of education, and limited healthcare infrastructure, play a critical role in determining who can access these resources.
Cultural considerations further complicate the social landscape, as varying beliefs about health, disease, and genetics can influence acceptance of testing and adherence to care. Vulnerable populations, including those in low-income settings or with limited social support, are disproportionately affected by these disparities, potentially deepening health inequities. From a global health perspective, the implications are even more pronounced, with vast differences in diagnostic capabilities, treatment availability, and ethical oversight across different regions, particularly in areas heavily burdened by the HIV epidemic.
Regulatory and Clinical Governance
Section titled “Regulatory and Clinical Governance”Effective policy and regulation are essential to navigate the ethical and social challenges posed by genetic research into AIDS dementia. This includes establishing stringent genetic testing regulations that dictate how tests are administered, interpreted, and communicated to patients, ensuring accuracy and minimizing harm. Comprehensive data protection frameworks are crucial to safeguard sensitive genetic and health information, preventing breaches and misuse that could lead to discrimination or privacy violations. These regulations must evolve alongside scientific advancements to address emerging ethical dilemmas.
Research ethics also demand continuous vigilance, particularly when involving vulnerable populations, ensuring that studies are conducted with the highest standards of integrity, transparency, and respect for participants. [1] Clear clinical guidelines are needed to integrate genetic findings into patient care in a responsible manner, advising healthcare providers on appropriate counseling, follow-up, and management strategies. Moreover, considerations of health equity and resource allocation are vital, ensuring that any benefits derived from genetic discoveries are distributed fairly and that interventions are accessible to all who need them, rather than exacerbating existing disparities.
Key Variants
Section titled “Key Variants”| RS ID | Gene | Related Traits |
|---|---|---|
| rs6857 | NECTIN2 | frontotemporal dementia neurofibrillary tangles measurement neuritic plaque measurement dementia, Alzheimer’s disease neuropathologic change cerebral amyloid angiopathy |
| rs429358 | APOE | cerebral amyloid deposition measurement Lewy body dementia, Lewy body dementia measurement high density lipoprotein cholesterol measurement platelet count neuroimaging measurement |
| rs4663105 rs744373 rs730482 | BIN1 - NIFKP9 | Alzheimer disease family history of Alzheimer’s disease Alzheimer disease, family history of Alzheimer’s disease late-onset Alzheimers disease Alzheimer’s disease biomarker measurement |
| rs2395029 | HCP5 | AIDS HIV-1 infection psoriasis drug-induced liver injury LCN2/PGLYRP1 protein level ratio in blood |
| rs556399519 | FGGY | drug use measurement, dementia |
| rs563910796 | MIATNB, MIAT | dementia |
| rs10402524 | BCAM - NECTIN2 | dementia memory performance |
| rs146791569 | OLFM1 - LINC02907 | drug use measurement, dementia |
| rs36113352 | NRP1 - LINC02628 | dementia |
| rs12453 rs2278867 | MS4A6A | Lewy body dementia dementia neutrophil count factor VII measurement Alzheimer disease, dementia, family history of Alzheimer’s disease |
Frequently Asked Questions About Aids Dementia
Section titled “Frequently Asked Questions About Aids Dementia”These questions address the most important and specific aspects of aids dementia based on current genetic research.
This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.
Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.
References
Section titled “References”[1] Levine, A. J., et al. “Genome-wide association study of neurocognitive impairment and dementia in HIV-infected adults.”American Journal of Medical Genetics - Part B - Neuropsychiatric Genetics, vol. 159, no. 5, 2012, pp. 586-591.
[2] Talyansky S et al. “APOE-ε4 and BIN1 increase risk of Alzheimer’s disease pathology but not specifically of Lewy body pathology.”Acta Neuropathol Commun, 2023.
[3] Fongang B et al. “A genome-wide association meta-analysis of all-cause and vascular dementia.”Alzheimers Dement, 2024.
[4] Zhang, Y. R., et al. “Whole exome sequencing analyses identified novel genes for Alzheimer’s disease and related dementia.”Alzheimer’s & Dementia, 2023.
[5] Ramirez, A., et al. “SUCLG2 identified as both a determinator of CSF Aβ1-42 levels and an attenuator of cognitive decline in Alzheimer’s disease.”Human Molecular Genetics, vol. 23, no. 20, 2014, pp. 5556-5563.
[6] Chung, J., et al. “Genome-wide association study of Alzheimer’s disease endophenotypes at prediagnosis stages.”Alzheimer’s & Dementia, vol. 14, no. 5, 2018, pp. 595-604.
[7] Lee, B., et al. “Genome-Wide association study of quantitative biomarkers identifies a novel locus for alzheimer’s disease at 12p12.1.”BMC Genomics, vol. 23, no. 1, 2022, p. 85.
[8] Le Borgne J et al. “X-chromosome-wide association study for Alzheimer’s disease.”Mol Psychiatry, 2024.
[9] Beecham, G. W., et al. “Genome-wide association meta-analysis of neuropathologic features of Alzheimer’s disease and related dementias.”PLoS Genetics, vol. 10, no. 9, 2014, e1004606.
[10] Chibnik, L. B., et al. “Susceptibility to neurofibrillary tangles: role of the PTPRD locus and limited pleiotropy with other neuropathologies.” Molecular Psychiatry, vol. 22, no. 10, 2017, pp. 1450-1457.
[11] Cochran JN et al. “Genetic associations with age at dementia onset in the PSEN1 E280A Colombian kindred.”Alzheimers Dement, 2023.
[12] Guo, P. et al. “Pinpointing novel risk loci for Lewy body dementia and the shared genetic etiology with Alzheimer’s disease and Parkinson’s disease: a large-scale multi-trait association analysis.”BMC Med, vol. 20, no. 1, 2022, p. 222.
[13] Bayram, Elif et al. “Genetic analysis of the X chromosome in people with Lewy body dementia nominates new risk loci.”NPJ Parkinsons Dis, vol. 10, no. 1, 2024, p. 30.
[14] Sherva, R., et al. “African ancestry GWAS of dementia in a large military cohort identifies significant risk loci.”Molecular Psychiatry, vol. 28, no. 3, 2023, pp. 1118-1129.