Limits...
Migration of blood cells to β-amyloid plaques in Alzheimer's disease.

Hohsfield LA, Humpel C - Exp. Gerontol. (2015)

Bottom Line: Alzheimer's disease (AD) is a neurodegenerative disease that leads to the progressive deterioration of cognitive and memory functions.The deposition of extracellular beta-amyloid (Aβ) senile plaques and intracellular tau neurofibrillary tangles are considered the cardinal pathological hallmarks of AD, however, accumulating evidence indicates that immune cells may also play an important role in disease pathogenesis.Here, we review the current literature on blood cell migration into the AD brain and the important players involved in this selective migration towards Aβ plaques.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Psychiatry and Experimental Alzheimer's Research, Department of Psychiatry and Psychotherapy, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.

No MeSH data available.


Related in: MedlinePlus

The migration of peripheral monocytes to beta-amyloid (Aβ) plaques in the AD brain. (A) A schematic rendering of fluorescent stainings (taken from our own laboratory) of an Aβ plaque with associated brain vessels. The Aβ core contains aggregated Aβ peptides, surrounded by reactive astrocytes and activated microglia. Monocytes migrate into the brain and may differentiate into macrophages or microglia. (B) A hypothetical rendering of monocyte recruitment into the AD brain. The recruitment of monocytes into the AD brain begins when Aβ deposition and associated neuronal damage triggers a local immune response activating astrocytes, endothelial cells, and microglia. This activation leads to the secretion of the chemokine CCL2, which recruits more immune effector cells (mainly CCR2+ monocytes) to the site of parenchymal Aβ deposition. Resident microglia appear to lose their ability to effectively phagocytose Aβ, however, blood-derived monocytes differentiate into macrophages, which are more effective at phagocytosis and clearing Aβ plaques. Although CCR2+ inflammatory monocytes have become the primary monocyte subpopulation implicated in providing therapeutic benefits to the AD brain, recent data indicates that CX3CR1hi resident monocytes may be responsible for clearing vascular Aβ deposition.This cartoon B has been partly adapted and modified from others: Britschgi and Wyss-Coray (2007), El Khoury and Luster (2008), Gate et al. (2010), Hickman and El Khoury (2010), Malm et al. (2010), Michaud et al. (2013), Mildner et al. (2011).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4526125&req=5

Figure 1: The migration of peripheral monocytes to beta-amyloid (Aβ) plaques in the AD brain. (A) A schematic rendering of fluorescent stainings (taken from our own laboratory) of an Aβ plaque with associated brain vessels. The Aβ core contains aggregated Aβ peptides, surrounded by reactive astrocytes and activated microglia. Monocytes migrate into the brain and may differentiate into macrophages or microglia. (B) A hypothetical rendering of monocyte recruitment into the AD brain. The recruitment of monocytes into the AD brain begins when Aβ deposition and associated neuronal damage triggers a local immune response activating astrocytes, endothelial cells, and microglia. This activation leads to the secretion of the chemokine CCL2, which recruits more immune effector cells (mainly CCR2+ monocytes) to the site of parenchymal Aβ deposition. Resident microglia appear to lose their ability to effectively phagocytose Aβ, however, blood-derived monocytes differentiate into macrophages, which are more effective at phagocytosis and clearing Aβ plaques. Although CCR2+ inflammatory monocytes have become the primary monocyte subpopulation implicated in providing therapeutic benefits to the AD brain, recent data indicates that CX3CR1hi resident monocytes may be responsible for clearing vascular Aβ deposition.This cartoon B has been partly adapted and modified from others: Britschgi and Wyss-Coray (2007), El Khoury and Luster (2008), Gate et al. (2010), Hickman and El Khoury (2010), Malm et al. (2010), Michaud et al. (2013), Mildner et al. (2011).

Mentions: Alzheimer’s disease (AD) is characterized by the presence of extracellular senile beta-amyloid (Aβ) plaques and intracellular neurofibrillary tau tangles, however, other disease pathology features include the loss of cholinergic neurons and synapses, the loss of white matter, congophilic/cerebral amyloid angiopathy (CAA), inflammation, oxidative stress and cerebrovascular dysfunction (Mufson et al., 2008; Perl, 2010; Querfurth and LaFerla, 2010; Serrano-Pozo et al., 2011). Senile plaques are primarily composed of Aβ peptides, byproducts of amyloid precursor protein (APP) metabolism following its sequential cleavage by the enzymes β- and γ-secretase, which results in the generation of two Aβ species: Aβ40 and Aβ42 (LaFerla et al., 2007). Aβ40 is the more prevalent isoform found in vivo and serves as a major component of CAA (LaFerla et al., 2007; Serrano-Pozo et al., 2011). Aβ42 makes up only 10% of the total Aβ, but is the more predominant toxic species found in plaques due to its enhanced hydrophobicity, aggregation and fibrillization potential. It can spontaneously self-aggregate to generate soluble neurotoxic oligomers or insoluble fibrils that form plaques (LaFerla et al., 2007; Querfurth and LaFerla, 2010). Neuritic or dense-core senile plaques contain Aβ fibrils arranged radially into a central core. More importantly, these plaques are typically surrounded by dystrophic neurites, reactive astrocytes, activated microglial cells, and synaptic loss, indicating that these cells may play an important role in disease pathology (Fig. 1A). Abnormal mitochondria and lysosomes have also been found within these activated cells, indicating that energy or protein degradation processes may be compromised. In addition, there is also evidence that Aβ plaques are directly associated with brain vessels, indicating that blood vessel proximity may play a role in plaque formation and/or remodeling (Kumar-Singh et al., 2005).


Migration of blood cells to β-amyloid plaques in Alzheimer's disease.

Hohsfield LA, Humpel C - Exp. Gerontol. (2015)

The migration of peripheral monocytes to beta-amyloid (Aβ) plaques in the AD brain. (A) A schematic rendering of fluorescent stainings (taken from our own laboratory) of an Aβ plaque with associated brain vessels. The Aβ core contains aggregated Aβ peptides, surrounded by reactive astrocytes and activated microglia. Monocytes migrate into the brain and may differentiate into macrophages or microglia. (B) A hypothetical rendering of monocyte recruitment into the AD brain. The recruitment of monocytes into the AD brain begins when Aβ deposition and associated neuronal damage triggers a local immune response activating astrocytes, endothelial cells, and microglia. This activation leads to the secretion of the chemokine CCL2, which recruits more immune effector cells (mainly CCR2+ monocytes) to the site of parenchymal Aβ deposition. Resident microglia appear to lose their ability to effectively phagocytose Aβ, however, blood-derived monocytes differentiate into macrophages, which are more effective at phagocytosis and clearing Aβ plaques. Although CCR2+ inflammatory monocytes have become the primary monocyte subpopulation implicated in providing therapeutic benefits to the AD brain, recent data indicates that CX3CR1hi resident monocytes may be responsible for clearing vascular Aβ deposition.This cartoon B has been partly adapted and modified from others: Britschgi and Wyss-Coray (2007), El Khoury and Luster (2008), Gate et al. (2010), Hickman and El Khoury (2010), Malm et al. (2010), Michaud et al. (2013), Mildner et al. (2011).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526125&req=5

Figure 1: The migration of peripheral monocytes to beta-amyloid (Aβ) plaques in the AD brain. (A) A schematic rendering of fluorescent stainings (taken from our own laboratory) of an Aβ plaque with associated brain vessels. The Aβ core contains aggregated Aβ peptides, surrounded by reactive astrocytes and activated microglia. Monocytes migrate into the brain and may differentiate into macrophages or microglia. (B) A hypothetical rendering of monocyte recruitment into the AD brain. The recruitment of monocytes into the AD brain begins when Aβ deposition and associated neuronal damage triggers a local immune response activating astrocytes, endothelial cells, and microglia. This activation leads to the secretion of the chemokine CCL2, which recruits more immune effector cells (mainly CCR2+ monocytes) to the site of parenchymal Aβ deposition. Resident microglia appear to lose their ability to effectively phagocytose Aβ, however, blood-derived monocytes differentiate into macrophages, which are more effective at phagocytosis and clearing Aβ plaques. Although CCR2+ inflammatory monocytes have become the primary monocyte subpopulation implicated in providing therapeutic benefits to the AD brain, recent data indicates that CX3CR1hi resident monocytes may be responsible for clearing vascular Aβ deposition.This cartoon B has been partly adapted and modified from others: Britschgi and Wyss-Coray (2007), El Khoury and Luster (2008), Gate et al. (2010), Hickman and El Khoury (2010), Malm et al. (2010), Michaud et al. (2013), Mildner et al. (2011).
Mentions: Alzheimer’s disease (AD) is characterized by the presence of extracellular senile beta-amyloid (Aβ) plaques and intracellular neurofibrillary tau tangles, however, other disease pathology features include the loss of cholinergic neurons and synapses, the loss of white matter, congophilic/cerebral amyloid angiopathy (CAA), inflammation, oxidative stress and cerebrovascular dysfunction (Mufson et al., 2008; Perl, 2010; Querfurth and LaFerla, 2010; Serrano-Pozo et al., 2011). Senile plaques are primarily composed of Aβ peptides, byproducts of amyloid precursor protein (APP) metabolism following its sequential cleavage by the enzymes β- and γ-secretase, which results in the generation of two Aβ species: Aβ40 and Aβ42 (LaFerla et al., 2007). Aβ40 is the more prevalent isoform found in vivo and serves as a major component of CAA (LaFerla et al., 2007; Serrano-Pozo et al., 2011). Aβ42 makes up only 10% of the total Aβ, but is the more predominant toxic species found in plaques due to its enhanced hydrophobicity, aggregation and fibrillization potential. It can spontaneously self-aggregate to generate soluble neurotoxic oligomers or insoluble fibrils that form plaques (LaFerla et al., 2007; Querfurth and LaFerla, 2010). Neuritic or dense-core senile plaques contain Aβ fibrils arranged radially into a central core. More importantly, these plaques are typically surrounded by dystrophic neurites, reactive astrocytes, activated microglial cells, and synaptic loss, indicating that these cells may play an important role in disease pathology (Fig. 1A). Abnormal mitochondria and lysosomes have also been found within these activated cells, indicating that energy or protein degradation processes may be compromised. In addition, there is also evidence that Aβ plaques are directly associated with brain vessels, indicating that blood vessel proximity may play a role in plaque formation and/or remodeling (Kumar-Singh et al., 2005).

Bottom Line: Alzheimer's disease (AD) is a neurodegenerative disease that leads to the progressive deterioration of cognitive and memory functions.The deposition of extracellular beta-amyloid (Aβ) senile plaques and intracellular tau neurofibrillary tangles are considered the cardinal pathological hallmarks of AD, however, accumulating evidence indicates that immune cells may also play an important role in disease pathogenesis.Here, we review the current literature on blood cell migration into the AD brain and the important players involved in this selective migration towards Aβ plaques.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Psychiatry and Experimental Alzheimer's Research, Department of Psychiatry and Psychotherapy, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.

No MeSH data available.


Related in: MedlinePlus