Blood cell-produced amyloid-β induces cerebral Alzheimer-type pathologies and behavioral deficits

Sun, Hao‐Lun; Chen, Sihan; Yu, Zhongyuan; Cheng, Yuan; Tian, Ding-Yuan; Fan, Dong-Yu; He, Chenyang; Wang, Jun; Sun, Pu‐Yang; Cs, Yang; Tan, Cheng‐Rong; Wang, Junping; Song, Weihong; Zhou, Huadong; Chen, Xiaowei; Hu, Zhian; Bu, Xian‐Le; Wang, Yanjiang

doi:10.1038/s41380-020-0842-1

Cited by 43 publications

(40 citation statements)

References 39 publications

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“…The population of the developed world is aging, and the incidence of age-related metabolic and neurodegenerative diseases is increasing. Alzheimer’s disease (AD) is one of the most common age-associated neurodegenerative diseases; it is characterized by the accumulation of extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles (NFTs; Jack, 2020 ; Sun et al, 2020 ). Mutations in one or more of the genes that encode amyloid precursor protein (APP), presenilin 1 (PS1), or presenilin 2 (PS2) represent genetic risk factors for AD (Gaiteri et al, 2016 ) and are typically associated with early-onset AD, but account for less than half of all cases.…”

Section: Introductionmentioning

confidence: 99%

Exploiting Common Aspects of Obesity and Alzheimer’s Disease

Tabassum

Misrani

Yang

2020

Front. Hum. Neurosci.

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Alzheimer’s disease (AD) is an example of age-related dementia, and there are still no known preventive or curative measures for this disease. Obesity and associated metabolic changes are widely accepted as risk factors of age-related cognitive decline. Insulin is the prime mediator of metabolic homeostasis, which is impaired in obesity, and this impairment potentiates amyloid-β (Aβ) accumulation and the formation of neurofibrillary tangles (NFTs). Obesity is also linked with functional and morphological alterations in brain mitochondria leading to brain insulin resistance (IR) and memory deficits associated with AD. Also, increased peripheral inflammation and oxidative stress due to obesity are the main drivers that increase an individual’s susceptibility to cognitive deficits, thus doubling the risk of AD. This enhanced risk of AD is alarming in the context of a rapidly increasing global incidence of obesity and overweight in the general population. In this review, we summarize the risk factors that link obesity with AD and emphasize the point that the treatment and management of obesity may also provide a way to prevent AD.

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Section: Introductionmentioning

confidence: 99%

Exploiting Common Aspects of Obesity and Alzheimer’s Disease

Tabassum

Misrani

Yang

2020

Front. Hum. Neurosci.

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“…We found that the capacity of macrophages to phagocytose Aβ 1−42 in Tg mice and Wt mice, paWt(Wt-Tg) mice and paWt(Wt-Wt) mice, showed no signi cant difference both in animals aged 7 months and 11 months; however, the phagocytosis ability of macrophages was increased after in vitro Aβ 1−42 peptide coculture. In a previous study, Aβ was found to be an effective stimulant of macrophage/microglia phagocytosis [43]. However, the phagocytosis ability of macrophage/microglia in AD patients is controversial and complicated.…”

Section: Discussionmentioning

confidence: 95%

High Plasma Llevels of Aβ1-42 Affect Monocytes and Macrophages via Biphasic Effects on Myeloid-Derived Suppressor Cells and Granulocyte-Monocyte Progenitors in Mouse Models of Alzheimer’s Disease

Liu

Zhu

et al. 2021

Preprint

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Backgroud: Microglia play a crucial role in the pathogenesis of Alzheimer’s disease (AD). Plasma Aβ1-42 levels significantly increase 15 years before the onset of dominantly inherited AD. The effects of high plasma levels of Aβ1-42 on monocytes and macrophages, the hematogenous counterparts of microglia, remain unclear. Methods: We investigated the effects of plasma Aβ1-42 on peripheral monocytes and macrophages in three animal models, including 7- and 11-month-old female APPswe/PS1dE9 (APP/PS1) transgenic (Tg) mice, wild-type (Wt) parabiotic with Tg (paWt(Wt-Tg)) mice, and Wt mice. Results: We found that high plasma levels of Aβ1-42, in younger (7-month) AD mice significantly decreased the amounts of pro-inflammatory macrophages, myeloid derived suppressor cells (MDSCs), granulocyte-monocyte progenitors (GMP), and the plasma levels of interleukin-6 (IL-6). In older (11-month) AD mice, high plasma levels of Aβ1-42 significantly increased the amounts of pro-inflammatory macrophages, MDSCs, GMPs, the plasma levels of IL-6 and TNF-α, and the brain infiltration of bone marrow-derived macrophages (BMDMs). However, high plasma levels of Aβ1-42 consistently increased the amounts of monocytes and the proliferation of bone marrow cells (BMCs) without affecting the phagocytic function of macrophages on Aβ1-42. Conclusion: The response of mouse AD model suggests that a high plasma level of Aβ1-42 affects monocytes and macrophages via its biphasic effects on MDSCs and GMPs. We suggest that intervening in the effects of plasma Aβ1-42 on monocytes and macrophages might offer a new therapeutic approach to AD.

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“…In terms of predicting whether patients with MCI will convert to AD, no consistent data on plasma Aβ1-42, Aβ1-40, or ratios have been reported [9,39,40]. Data variability is often due to sampling variability regarding subject age and/or disease severity [39,44], but may also be related to plasma Aβ levels, e.g., an individual's peripheral clearance of Aβ [50], hemoglobin levels [25], apolipoprotein E genotype [26], or platelet levels [51]. Whether age is a factor to plasma amyloid level, the association of age and increased plasma Aβ and reduced Aβ1-40 / Aβ1-42 ratio was primarily restricted to MCI patients or individuals with worsening cognitive status [9].…”

Section: Pitfalls In Detecting Amyloid Plasma Levelsmentioning

confidence: 99%

Can blood amyloid levels be used as a biomarker for Alzheimer’s disease?

Yang

Situmeang

Ong

2021

Brain Science Advances

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Alzheimer’s disease (AD) increasingly affects society due to aging populations. Even at pre‐clinical stages, earlier and accurate diagnoses are essential for optimal AD management and improved clinical outcomes. Biomarkers such as beta‐amyloid (Aβ) or tau protein in cerebrospinal fluid (CSF) have been used as reliable markers to distinguish AD from non‐AD, and predicting clinical outcomes, to attain these goals. However, given CSF access methods’ invasiveness, these biomarkers are not used extensively in clinical settings. Blood Aβ has been proposed as an alternative biomarker since it is less invasive than CSF; however, sampling heterogeneity has limited its clinical applicability. In this review, we investigated blood Aβ as a biomarker in AD and explored how Aβ can be facilitated as a viable biomarker for successful AD management.

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Blood cell-produced amyloid-β induces cerebral Alzheimer-type pathologies and behavioral deficits

Cited by 43 publications

References 39 publications

Exploiting Common Aspects of Obesity and Alzheimer’s Disease

Exploiting Common Aspects of Obesity and Alzheimer’s Disease

High Plasma Llevels of Aβ1-42 Affect Monocytes and Macrophages via Biphasic Effects on Myeloid-Derived Suppressor Cells and Granulocyte-Monocyte Progenitors in Mouse Models of Alzheimer’s Disease

Can blood amyloid levels be used as a biomarker for Alzheimer’s disease?

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