O3‐06‐01: Vascular amyloidosis impairs the gliovascular unit in a mouse model of Alzheimer's disease

Kimbrough, Ian F.; Robel, Stefanie; Roberson, Erik D.; Sontheimer, Harald

doi:10.1016/j.jalz.2015.07.267

Cited by 10 publications

(9 citation statements)

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“…Amyloid deposition in the neocortex likely triggered the higher astrogliosis observed in these regions, as activated astrocytes typically surround amyloid plaques (Beach & McGeer, 1988;Beach et al,1989;DeWitt, Perry, Cohen, Doller, & Silver, 1998;Duffy et al, 1980;Kimbrough et al, 2015;Mancardi et al, 1983;Mandybur, 1989;Nagele et al, 2004;Schechter et al, 1981;Rodríguez et al, 2009). Much of the astrogliosis we observed occurred in relation to vasculature pathology.…”

Section: Discussionmentioning

confidence: 99%

Astrocytic changes with aging and Alzheimer's disease‐type pathology in chimpanzees

Munger

Edler

Hopkins³

et al. 2019

J of Comparative Neurology

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Astrocytes are the main homeostatic cell of the central nervous system. In addition, astrocytes mediate an inflammatory response when reactive to injury or disease known as astrogliosis. Astrogliosis is marked by an increased expression of glial fibrillary acidic protein (GFAP) and cellular hypertrophy. Some degree of astrogliosis is associated with normal aging and degenerative conditions such as Alzheimer's disease (AD) and other dementing illnesses in humans. The recent observation of pathological markers of AD (amyloid plaques and neurofibrillary tangles) in aged chimpanzee brains provided an opportunity to examine the relationships among aging, AD‐type pathology, and astrocyte activation in our closest living relatives. Stereologic methods were used to quantify GFAP‐immunoreactive astrocyte density and soma volume in layers I, III, and V of the prefrontal and middle temporal cortex, as well as in hippocampal fields CA1 and CA3. We found that the patterns of astrocyte activation in the aged chimpanzee brain are distinct from humans. GFAP expression does not increase with age in chimpanzees, possibly indicative of lower oxidative stress loads. Similar to humans, chimpanzee layer I astrocytes in the prefrontal cortex are susceptible to AD‐like changes. Both prefrontal cortex layer I and hippocampal astrocytes exhibit a high degree of astrogliosis that is positively correlated with accumulation of amyloid beta and tau proteins. However, unlike humans, chimpanzees do not display astrogliosis in other cortical layers. These results demonstrate a unique pattern of cortical aging in chimpanzees and suggest that inflammatory processes may differ between humans and chimpanzees in response to pathology.

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Section: Discussionmentioning

confidence: 99%

Astrocytic changes with aging and Alzheimer's disease‐type pathology in chimpanzees

Munger

Edler

Hopkins³

et al. 2019

J of Comparative Neurology

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“…As retinal and cerebral microvasculature share many morphological and physiological properties (34), these vascular amyloid findings may explain the well-documented narrowing of venous blood column diameter and reduced blood flow in both the retinas (19,20,33,76,92) and brains (93)(94)(95) of AD patients. Recently, a mechanism for such phenomena was proposed in a study using murine models of AD demonstrating that vascular amyloid could harden blood vessel walls and decrease blood flow (96). Still, larger studies are required to confirm the association between cerebral amyloid angiopathy and retinal vascular amyloid pathology.…”

Section: Discussionmentioning

confidence: 99%

Retinal amyloid pathology and proof-of-concept imaging trial in Alzheimer’s disease

et al. 2017

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BACKGROUND. Noninvasive detection of Alzheimer's disease (AD) with high specificity and sensitivity can greatly facilitate identification of at-risk populations for earlier, more effective intervention. AD patients exhibit a myriad of retinal pathologies, including hallmark amyloid β-protein (Aβ) deposits. METHODS.Burden, distribution, cellular layer, and structure of retinal Aβ plaques were analyzed in flat mounts and cross sections of definite AD patients and controls (n = 37). In a proof-of-concept retinal imaging trial (n = 16), amyloid probe curcumin formulation was determined and protocol was established for retinal amyloid imaging in live patients. RESULTS.Histological examination uncovered classical and neuritic-like Aβ deposits with increased retinal Aβ 42 plaques (4.7-fold; P = 0.0063) and neuronal loss (P = 0.0023) in AD patients versus matched controls. Retinal Aβ plaque mirrored brain pathology, especially in the primary visual cortex (P = 0.0097 to P = 0.0018; Pearson's r = 0.84-0.91). Retinal deposits often associated with blood vessels and occurred in hot spot peripheral regions of the superior quadrant and innermost retinal layers. Transmission electron microscopy revealed retinal Aβ assembled into protofibrils and fibrils. Moreover, the ability to image retinal amyloid deposits with solid-lipid curcumin and a modified scanning laser ophthalmoscope was demonstrated in live patients. A fully automated calculation of the retinal amyloid index (RAI), a quantitative measure of increased curcumin fluorescence, was constructed. Analysis of RAI scores showed a 2.1-fold increase in AD patients versus controls (P = 0.0031). CONCLUSION.The geometric distribution and increased burden of retinal amyloid pathology in AD, together with the feasibility to noninvasively detect discrete retinal amyloid deposits in living patients, may lead to a practical approach for large-scale AD diagnosis and monitoring.

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“…In endfeet, Aqp4 loses its polarization at amyloid deposition sites (Yang et al, 2011). In capillary cerebral amyloid angiopathy (CAA), the amyloid deposits can form a ring around the vessel; this separates the endfeet from the endothelial vessel wall and alters the astrocytic Ca 2+ ‐mediated hyperemic responses (Kimbrough, Robel, Roberson, & Sontheimer, 2015). CAA also causes the loss of Kir4.1 and dystrophin expression, which in turn perturbs potassium homeostasis and the mechanical and functional links between astrocytes and other cellular components of the gliovascular interface (Wilcock, Vitek, & Colton, 2009).…”

Section: The Gliovascular Interface In Brain Diseasesmentioning

confidence: 99%

Astrocytes in the regulation of cerebrovascular functions

Cohen-Salmon

Slaoui

Mazaré

et al. 2020

Glia

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Astrocytes are the most numerous type of neuroglia in the brain and have a predominant influence on the cerebrovascular system; they control perivascular homeostasis, the integrity of the blood–brain barrier, the dialogue with the peripheral immune system, the transfer of metabolites from the blood, and blood vessel contractility in response to neuronal activity. These regulatory processes occur in a specialized interface composed of perivascular astrocyte extensions that almost completely cover the cerebral blood vessels. Scientists have only recently started to study how this interface is formed and how it influences cerebrovascular functions. Here, we review the literature on the astrocytes' role in the regulation of the cerebrovascular system. We cover the anatomy and development of the gliovascular interface, the known gliovascular functions, and molecular factors, the latter's implication in certain pathophysiological situations, and recent cutting‐edge experimental tools developed to examine the astrocytes' role at the vascular interface. Finally, we highlight some open questions in this field of research.

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O3‐06‐01: Vascular amyloidosis impairs the gliovascular unit in a mouse model of Alzheimer's disease

Cited by 10 publications

References 0 publications

Astrocytic changes with aging and Alzheimer's disease‐type pathology in chimpanzees

Astrocytic changes with aging and Alzheimer's disease‐type pathology in chimpanzees

Retinal amyloid pathology and proof-of-concept imaging trial in Alzheimer’s disease

Astrocytes in the regulation of cerebrovascular functions

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