Occurrence and co-localization of amyloid β-protein and apolipoprotein E in perivascular drainage channels of wild-type and APP-transgenic mice

Thal, Dietmar Rudolf; Larionov, Sergey; Abramowski, Dorothée; Wiederhold, Karl‐Heinz; Dooren, Tom Van; Yamaguchi, Hideyo; Haass, Christian; Leuven, Freddy Van; Staufenbiel, Matthias; Capetillo-Zárate, Estibaliz

doi:10.1016/j.neurobiolaging.2006.05.029

Cited by 54 publications

(50 citation statements)

References 37 publications

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“…By contrast, fibronectin and perlecan were significantly increased with age in blood vessels in the cortex, striatum, and hippocampus. These findings support the suggestion that with increasing age, there may be a relative decrease in the ratio of individual basement membrane proteins that inhibit and promote Ab aggregation, leading to a failure of perivascular drainage of Ab and other solutes which accumulate in the cerebrovascular basement membranes (Revesz et al, 2003;Thal et al, 2007;Weller et al, 2008).…”

Section: Discussionsupporting

confidence: 86%

Regional differences in the morphological and functional effects of aging on cerebral basement membranes and perivascular drainage of amyloid‐β from the mouse brain

et al. 2013

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SummaryDevelopment of cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD) is associated with failure of elimination of amyloid-b (Ab) from the brain along perivascular basement membranes that form the pathways for drainage of interstitial fluid and solutes from the brain. In transgenic APP mouse models of AD, the severity of cerebral amyloid angiopathy is greater in the cerebral cortex and hippocampus, intermediate in the thalamus, and least in the striatum. In this study we test the hypothesis that age-related regional variation in (1) vascular basement membranes and (2) perivascular drainage of Ab contribute to the different regional patterns of CAA in the mouse brain. Quantitative electron microscopy of the brains of 2-, 7-, and 23-month-old mice revealed significant age-related thickening of capillary basement membranes in cerebral cortex, hippocampus, and thalamus, but not in the striatum. Results from Western blotting and immunocytochemistry experiments showed a significant reduction in collagen IV in the cortex and hippocampus with age and a reduction in laminin and nidogen 2 in the cortex and striatum. Injection of soluble Ab into the hippocampus or thalamus showed an agerelated reduction in perivascular drainage from the hippocampus but not from the thalamus. The results of the study suggest that changes in vascular basement membranes and perivascular drainage with age differ between brain regions, in the mouse, in a manner that may help to explain the differential deposition of Ab in the brain in AD and may facilitate development of improved therapeutic strategies to remove Ab from the brain in AD.

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Section: Discussionsupporting

confidence: 86%

Regional differences in the morphological and functional effects of aging on cerebral basement membranes and perivascular drainage of amyloid‐β from the mouse brain

et al. 2013

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“…Before the use of monoclonal mouse antibodies, 100-m-thick free-floating sections were incubated with goat anti-mouse IgG for blocking intrinsic mouse IgG (Thal et al, 2007). To detect A␤ 1-42 -positive material, the sections were stained with monoclonal antibodies specifically detecting the C terminus of A␤ 42 [MBC42 (Yamaguchi et al, 1998); 1/200; formic acid pretreatment; 24 h at 22°C] or with an antibody raised against A␤ 17-24 (4G8; Covance; 1/5000; formic acid pretreatment; 24 h at 22°C), with an antibody directed against the N terminus of A␤ 1-42 [A␤N1D (Saido et al, 1995); polyclonal rabbit; 1/100; formic acid and microwave pretreatment], and with anti-A␤N3pE (polyclonal rabbit; IBL; 1/100; formic acid and microwave pretreatment).…”

Section: Methodsmentioning

confidence: 99%

Transgenic Expression of Intraneuronal Aβ₄₂But Not Aβ₄₀Leads to Cellular Aβ Lesions, Degeneration, and Functional Impairment without Typical Alzheimer's Disease Pathology

Abramowski¹,

Rabe²,

Upadhaya³

et al. 2012

J. Neurosci.

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An early role of amyloid-␤ peptide (A␤) aggregation in Alzheimer's disease pathogenesis is well established. However, the contribution of intracellular or extracellular forms of A␤ to the neurodegenerative process is a subject of considerable debate. We here describe transgenic mice expressing A␤ 1-40 (APP47) and A␤ 1-42 (APP48) with a cleaved signal sequence to insert both peptides during synthesis into the endoplasmic reticulum. Although lower in transgene mRNA, APP48 mice reach a higher brain A␤ concentration. The reduced solubility and increased aggregation of A␤ 1-42 may impair its degradation. APP48 mice develop intracellular A␤ lesions in dendrites and lysosomes. The hippocampal neuron number is reduced already at young age. The brain weight decreases during aging in conjunction with severe white matter atrophy. The mice show a motor impairment. Only very few A␤ 1-40 lesions are found in APP47 mice. Neither APP47 nor APP48 nor the bigenic mice develop extracellular amyloid plaques. While intracellular membrane expression of A␤ 1-42 in APP48 mice does not lead to the AD-typical lesions, A␤ aggregates develop within cells accompanied by considerable neurodegeneration.

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“…In this light, alternative modes of seed trafficking, beyond passive diffusion and neuronal transport, should be considered. These include perivascular and paravascular flow (Weller et al 1998;Thal et al 2007;Iliff et al 2012) or uptake and transport by nonneuronal cells such as macrophages (Eisele et al 2009) (see below).…”

Section: Trafficking Of Ab Seeds Trafficking Within the Brainmentioning

confidence: 99%

The Prion-Like Properties of Amyloid-β Assemblies: Implications for Alzheimer's Disease

Walker

Schelle

Jucker

2016

Cold Spring Harb Perspect Med

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Occurrence and co-localization of amyloid β-protein and apolipoprotein E in perivascular drainage channels of wild-type and APP-transgenic mice

Cited by 54 publications

References 37 publications

Regional differences in the morphological and functional effects of aging on cerebral basement membranes and perivascular drainage of amyloid‐β from the mouse brain

Regional differences in the morphological and functional effects of aging on cerebral basement membranes and perivascular drainage of amyloid‐β from the mouse brain

Transgenic Expression of Intraneuronal Aβ₄₂But Not Aβ₄₀Leads to Cellular Aβ Lesions, Degeneration, and Functional Impairment without Typical Alzheimer's Disease Pathology

The Prion-Like Properties of Amyloid-β Assemblies: Implications for Alzheimer's Disease

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Occurrence and co-localization of amyloid β-protein and apolipoprotein E in perivascular drainage channels of wild-type and APP-transgenic mice

Cited by 54 publications

References 37 publications

Regional differences in the morphological and functional effects of aging on cerebral basement membranes and perivascular drainage of amyloid‐β from the mouse brain

Regional differences in the morphological and functional effects of aging on cerebral basement membranes and perivascular drainage of amyloid‐β from the mouse brain

Transgenic Expression of Intraneuronal Aβ42But Not Aβ40Leads to Cellular Aβ Lesions, Degeneration, and Functional Impairment without Typical Alzheimer's Disease Pathology

The Prion-Like Properties of Amyloid-β Assemblies: Implications for Alzheimer's Disease

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Product

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Transgenic Expression of Intraneuronal Aβ₄₂But Not Aβ₄₀Leads to Cellular Aβ Lesions, Degeneration, and Functional Impairment without Typical Alzheimer's Disease Pathology