Sex-based differences in effector cells of the adaptive immune system during Alzheimer's disease and related dementias

Lutshumba, Jenny; Wilcock, Donna M.; Monson, Nancy; Stowe, Ann M.

doi:10.1016/j.nbd.2023.106202

Cited by 6 publications

(5 citation statements)

References 235 publications

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“…Nearly two-thirds of AD patients are female, experiencing more pronounced cognitive impairment than males at an equivalent disease stage ( Levine et al, 2021 ; Zhu et al, 2021 ; Lansdell et al, 2023 ; Lutshumba et al, 2023 ). Although sex differences in AD dementia are evident, the underlying reasons remain unclear.…”

Section: Sex Differences In Alzheimer’s Diseasementioning

confidence: 99%

“…Although sex differences in AD dementia are evident, the underlying reasons remain unclear. Closing this knowledge gap is crucial, as comprehending mechanisms and genetics driving distinct susceptibility between AD-affected males and females informs personalized prevention and treatment strategies for this pervasive neurodegenerative concern ( Lutshumba et al, 2023 ). Therefore, this section provides current evidence on sex differences in AD, encompassing mechanisms, genetics, and therapeutic responses ( Figure 1 ).…”

Section: Sex Differences In Alzheimer’s Diseasementioning

confidence: 99%

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Sex differences in the relationship between depression and Alzheimer’s disease—mechanisms, genetics, and therapeutic opportunities

Chen,

Wang,

Liu

et al. 2024

Front. Aging Neurosci.

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Depression and Alzheimer’s disease (AD) are prevalent neuropsychiatric disorders with intriguing epidemiological overlaps. Their interrelation has recently garnered widespread attention. Empirical evidence indicates that depressive disorders significantly contribute to AD risk, and approximately a quarter of AD patients have comorbid major depressive disorder, which underscores the bidirectional link between AD and depression. A growing body of evidence substantiates pervasive sex differences in both AD and depression: both conditions exhibit a higher incidence among women than among men. However, the available literature on this topic is somewhat fragmented, with no comprehensive review that delineates sex disparities in the depression–AD correlation. In this review, we bridge these gaps by summarizing recent progress in understanding sex-based differences in mechanisms, genetics, and therapeutic prospects for depression and AD. Additionally, we outline key challenges in the field, holding potential for improving treatment precision and efficacy tailored to male and female patients’ distinct needs.

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Section: Sex Differences In Alzheimer’s Diseasementioning

confidence: 99%

Section: Sex Differences In Alzheimer’s Diseasementioning

confidence: 99%

Sex differences in the relationship between depression and Alzheimer’s disease—mechanisms, genetics, and therapeutic opportunities

Chen,

Wang,

Liu

et al. 2024

Front. Aging Neurosci.

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“…Therefore, regulatory T cells (Tregs) and Th2 cells have a neuroprotective effect. In contrast, Th1, Th17, cytotoxic T cells, natural killer (NK) cells mediate an accelerate progression of neuroinflammation, which can result in an exacerbated/accelerated neurodegeneration and an increased mortality risk [39][40][41][42]. Furthermore, they show different systemic levels.…”

Section: Clonotypic Immune Cells In Neuroinflammation and Ndmentioning

confidence: 99%

“…Furthermore, they show different systemic levels. Precisely, circulating Th17 cells have shown higher levels in subjects with mild cognitive impairment (MCI) in cognitively normal subjects or those with non-Alzheimer's MCI [42]. In contrast, circulating Th1 cells have been demonstrated to have higher levels in subjects with AD [43].…”

Section: Clonotypic Immune Cells In Neuroinflammation and Ndmentioning

confidence: 99%

Neuroinflammation and Neurodegenerative Diseases: How Much Do We Still Not Know?

Balistreri,

Monastero

2023

Brain Sciences

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The term “neuroinflammation” defines the typical inflammatory response of the brain closely related to the onset of many neurodegenerative diseases (NDs). Neuroinflammation is well known, but its mechanisms and pathways are not entirely comprehended. Some progresses have been achieved through many efforts and research. Consequently, new cellular and molecular mechanisms, diverse and conventional, are emerging. In listing some of those that will be the subject of our description and discussion, essential are the important roles of peripheral and infiltrated monocytes and clonotypic cells, alterations in the gut–brain axis, dysregulation of the apelinergic system, alterations in the endothelial glycocalyx of the endothelial component of neuronal vascular units, variations in expression of some genes and levels of the encoding molecules by the action of microRNAs (miRNAs), or other epigenetic factors and distinctive transcriptional factors, as well as the role of autophagy, ferroptosis, sex differences, and modifications in the circadian cycle. Such mechanisms can add significantly to understanding the complex etiological puzzle of neuroinflammation and ND. In addition, they could represent biomarkers and targets of ND, which is increasing in the elderly.

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“…Several excellent reviews have recently been written describing microglial sex differences in brain development, maintenance, disease, and in response to lifestyle influences [14][15][16][17][18][19][20][21]. Although microglia recruit and respond to the adaptive immune system, and this interaction is becoming progressively more appreciated, the adaptive immune system in AD has been recently reviewed elsewhere [22]. We will therefore focus this review on the most recent findings, situating and contextualizing them in a rapidly expanding field to provide a comprehensive view of sex differences in AD, highlighting the contribution of microglia to these differences (summarized in Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Minding the Gap: Exploring Neuroinflammatory and Microglial Sex Differences in Alzheimer’s Disease

Reed,

Keller-Norrell

2023

IJMS

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Research into Alzheimer’s Disease (AD) describes a link between AD and the resident immune cells of the brain, the microglia. Further, this suspected link is thought to have underlying sex effects, although the mechanisms of these effects are only just beginning to be understood. Many of these insights are the result of policies put in place by funding agencies such as the National Institutes of Health (NIH) to consider sex as a biological variable (SABV) and the move towards precision medicine due to continued lackluster therapeutic options. The purpose of this review is to provide an updated assessment of the current research that summarizes sex differences and the research pertaining to microglia and their varied responses in AD.

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Sex-based differences in effector cells of the adaptive immune system during Alzheimer's disease and related dementias

Cited by 6 publications

References 235 publications

Sex differences in the relationship between depression and Alzheimer’s disease—mechanisms, genetics, and therapeutic opportunities

Sex differences in the relationship between depression and Alzheimer’s disease—mechanisms, genetics, and therapeutic opportunities

Neuroinflammation and Neurodegenerative Diseases: How Much Do We Still Not Know?

Minding the Gap: Exploring Neuroinflammatory and Microglial Sex Differences in Alzheimer’s Disease

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