PMC:6582309 / 29053-32636 JSONTXT

{"project":"2_test","denotations":[{"id":"31249505-16170565-38601624","span":{"begin":425,"end":429},"obj":"16170565"},{"id":"31249505-30333009-38601625","span":{"begin":636,"end":640},"obj":"30333009"},{"id":"31249505-18184371-38601626","span":{"begin":797,"end":801},"obj":"18184371"},{"id":"31249505-10332828-38601627","span":{"begin":912,"end":916},"obj":"10332828"},{"id":"31249505-12146803-38601628","span":{"begin":1292,"end":1296},"obj":"12146803"},{"id":"31249505-1868335-38601629","span":{"begin":1427,"end":1431},"obj":"1868335"},{"id":"31249505-1329997-38601630","span":{"begin":1448,"end":1452},"obj":"1329997"},{"id":"31249505-10332828-38601631","span":{"begin":1469,"end":1473},"obj":"10332828"},{"id":"31249505-11016539-38601632","span":{"begin":1489,"end":1493},"obj":"11016539"},{"id":"31249505-25588378-38601633","span":{"begin":1518,"end":1522},"obj":"25588378"},{"id":"31249505-26247394-38601634","span":{"begin":1540,"end":1544},"obj":"26247394"},{"id":"31249505-26922972-38601635","span":{"begin":1560,"end":1564},"obj":"26922972"},{"id":"31249505-27669976-38601636","span":{"begin":1580,"end":1584},"obj":"27669976"},{"id":"31249505-29441010-38601637","span":{"begin":1604,"end":1608},"obj":"29441010"},{"id":"31249505-18184371-38601638","span":{"begin":1948,"end":1952},"obj":"18184371"},{"id":"31249505-22239863-38601639","span":{"begin":1971,"end":1975},"obj":"22239863"},{"id":"31249505-27669976-38601640","span":{"begin":2256,"end":2260},"obj":"27669976"},{"id":"31249505-26922972-38601641","span":{"begin":2360,"end":2364},"obj":"26922972"},{"id":"31249505-2385040-38601642","span":{"begin":2466,"end":2470},"obj":"2385040"},{"id":"31249505-30482198-38601643","span":{"begin":2621,"end":2625},"obj":"30482198"}],"text":"The Neuropathology of Cerebral Blood Vessels\nIn patients with AD, accumulation of Aβ is often observed in the walls of blood vessels in the brain. This is called CAA and is caused by pathological deposits of Aβ and other proteins in the cerebral arterioles and capillaries of the leptomeninges and cortex. It is considered as an early and integral part of AD pathogenesis and the prevalence of CAA in AD is over 70% (Attems, 2005). CAA is a risk factor for hemorrhagic stroke and contributes to AD dementia. Atherosclerosis may also cause cerebrovascular dysfunction that may lead to cognitive decline as well as stroke (Shabir et al., 2018). The accumulation of amyloid in the walls of blood vessels is common in elderly people, patients with CAA and in almost all patients with AD (Kumar-Singh, 2008). The most CAA affected brain regions are the leptomeninges and frontal and temporal cortices (Borràs et al., 1999) with Aβ deposits in arteries, arterioles, capillaries, venules, and veins. The CAA disease progresses from mild, to moderate to severe stage, this is from almost intact blood vessels with minor Aβ deposits to extensive vascular Aβ load, which disrupts vessel architecture and exacerbates microangiopathies, microaneurysmal dilatation, and fibrinoid necrosis (Revesz et al., 2002).\nIn aged dogs Aβ deposits are detected both in the brain parenchyma and in the walls of cerebral blood vessels (Ishihara et al., 1991; Uchida et al., 1992; Borràs et al., 1999; Colle et al., 2000; Brettschneider et al., 2015; Schmidt et al., 2015; Ozawa et al., 2016; Nešić et al., 2017; Rusbridge et al., 2018), further suggesting similarities between AD in humans and CCD in dogs (Figures 2, 3). The amyloidotic blood vessels in the brains of dogs were observed by Congo red stainings as well as by antibodies directed against Aβ. Vascular Aβ deposition mainly consists of Aβ40 in humans, but both Aβ40 and Aβ42 were detected in dogs (Kumar-Singh, 2008; Chambers et al., 2012). In canine CAA, the most affected region is the frontal cortex, where Aβ is often present in microvascular parenchymal lesions in elderly dogs. In dogs with CCD an overlap between the density and anatomical distribution of CAA and parenchymal plaques was observed (Nešić et al., 2017). The CAA consistently increased with age, but did not correlate with the CCD score (Ozawa et al., 2016). Intracerebral hemorrhages have also been described in association with CAA in dogs (Uchida et al., 1990). A recent case reported multiple infarcts and brain hemorrhages in a dog with CAA and CCD, with cerebral and vascular Aβ deposits (Rodrigues et al., 2018). Pathological hallmarks of CCD and AD are summarized in Table 2.\nFIGURE 3 Amyloid beta (red) detected by immunofluorescence staining in the wall of a leptomeningeal blood vessel in the frontal cortex from a 15-years-old Pit Bull Terrier. Nuclei were counterstained with DAPI (blue). The antibody employed is the same as in Figure 2. Original microphotograph made by the authors.\nTABLE 2 Pathological hallmarks of CCD and/or AD.\nAbnormality CCD AD\nCognitive decline + +\nBrain atrophy + +\nNeuronal damage and death + +\nAβ accumulation in brain parenchyma + +\nDiffuse Aβ plaques + +\nDense-core Aβ plaques − +\nAβ accumulation in blood vessel walls (CAA) + +\nNeurofibrillary tangles (NTFs) formation − +\nMicroglial dysfunction + +\nAstrocyte dysfunction + +\nAstroglial hypertrophy and hyperplasia + +\nOxidative brain damage + +\nMitochondrial dysfunction + +\nCholinergic dysfunction + +\nImpaired neuronal glucose metabolism + +"}

{"project":"0_colil","denotations":[{"id":"31249505-16170565-737049","span":{"begin":425,"end":429},"obj":"16170565"},{"id":"31249505-30333009-737050","span":{"begin":636,"end":640},"obj":"30333009"},{"id":"31249505-18184371-737051","span":{"begin":797,"end":801},"obj":"18184371"},{"id":"31249505-10332828-737052","span":{"begin":912,"end":916},"obj":"10332828"},{"id":"31249505-12146803-737053","span":{"begin":1292,"end":1296},"obj":"12146803"},{"id":"31249505-1868335-737054","span":{"begin":1427,"end":1431},"obj":"1868335"},{"id":"31249505-1329997-737055","span":{"begin":1448,"end":1452},"obj":"1329997"},{"id":"31249505-10332828-737056","span":{"begin":1469,"end":1473},"obj":"10332828"},{"id":"31249505-11016539-737057","span":{"begin":1489,"end":1493},"obj":"11016539"},{"id":"31249505-25588378-737058","span":{"begin":1518,"end":1522},"obj":"25588378"},{"id":"31249505-26247394-737059","span":{"begin":1540,"end":1544},"obj":"26247394"},{"id":"31249505-26922972-737060","span":{"begin":1560,"end":1564},"obj":"26922972"},{"id":"31249505-27669976-737061","span":{"begin":1580,"end":1584},"obj":"27669976"},{"id":"31249505-29441010-737062","span":{"begin":1604,"end":1608},"obj":"29441010"},{"id":"31249505-18184371-737063","span":{"begin":1948,"end":1952},"obj":"18184371"},{"id":"31249505-22239863-737064","span":{"begin":1971,"end":1975},"obj":"22239863"},{"id":"31249505-27669976-737065","span":{"begin":2256,"end":2260},"obj":"27669976"},{"id":"31249505-26922972-737066","span":{"begin":2360,"end":2364},"obj":"26922972"},{"id":"31249505-2385040-737067","span":{"begin":2466,"end":2470},"obj":"2385040"},{"id":"31249505-30482198-737068","span":{"begin":2621,"end":2625},"obj":"30482198"}],"text":"The Neuropathology of Cerebral Blood Vessels\nIn patients with AD, accumulation of Aβ is often observed in the walls of blood vessels in the brain. This is called CAA and is caused by pathological deposits of Aβ and other proteins in the cerebral arterioles and capillaries of the leptomeninges and cortex. It is considered as an early and integral part of AD pathogenesis and the prevalence of CAA in AD is over 70% (Attems, 2005). CAA is a risk factor for hemorrhagic stroke and contributes to AD dementia. Atherosclerosis may also cause cerebrovascular dysfunction that may lead to cognitive decline as well as stroke (Shabir et al., 2018). The accumulation of amyloid in the walls of blood vessels is common in elderly people, patients with CAA and in almost all patients with AD (Kumar-Singh, 2008). The most CAA affected brain regions are the leptomeninges and frontal and temporal cortices (Borràs et al., 1999) with Aβ deposits in arteries, arterioles, capillaries, venules, and veins. The CAA disease progresses from mild, to moderate to severe stage, this is from almost intact blood vessels with minor Aβ deposits to extensive vascular Aβ load, which disrupts vessel architecture and exacerbates microangiopathies, microaneurysmal dilatation, and fibrinoid necrosis (Revesz et al., 2002).\nIn aged dogs Aβ deposits are detected both in the brain parenchyma and in the walls of cerebral blood vessels (Ishihara et al., 1991; Uchida et al., 1992; Borràs et al., 1999; Colle et al., 2000; Brettschneider et al., 2015; Schmidt et al., 2015; Ozawa et al., 2016; Nešić et al., 2017; Rusbridge et al., 2018), further suggesting similarities between AD in humans and CCD in dogs (Figures 2, 3). The amyloidotic blood vessels in the brains of dogs were observed by Congo red stainings as well as by antibodies directed against Aβ. Vascular Aβ deposition mainly consists of Aβ40 in humans, but both Aβ40 and Aβ42 were detected in dogs (Kumar-Singh, 2008; Chambers et al., 2012). In canine CAA, the most affected region is the frontal cortex, where Aβ is often present in microvascular parenchymal lesions in elderly dogs. In dogs with CCD an overlap between the density and anatomical distribution of CAA and parenchymal plaques was observed (Nešić et al., 2017). The CAA consistently increased with age, but did not correlate with the CCD score (Ozawa et al., 2016). Intracerebral hemorrhages have also been described in association with CAA in dogs (Uchida et al., 1990). A recent case reported multiple infarcts and brain hemorrhages in a dog with CAA and CCD, with cerebral and vascular Aβ deposits (Rodrigues et al., 2018). Pathological hallmarks of CCD and AD are summarized in Table 2.\nFIGURE 3 Amyloid beta (red) detected by immunofluorescence staining in the wall of a leptomeningeal blood vessel in the frontal cortex from a 15-years-old Pit Bull Terrier. Nuclei were counterstained with DAPI (blue). The antibody employed is the same as in Figure 2. Original microphotograph made by the authors.\nTABLE 2 Pathological hallmarks of CCD and/or AD.\nAbnormality CCD AD\nCognitive decline + +\nBrain atrophy + +\nNeuronal damage and death + +\nAβ accumulation in brain parenchyma + +\nDiffuse Aβ plaques + +\nDense-core Aβ plaques − +\nAβ accumulation in blood vessel walls (CAA) + +\nNeurofibrillary tangles (NTFs) formation − +\nMicroglial dysfunction + +\nAstrocyte dysfunction + +\nAstroglial hypertrophy and hyperplasia + +\nOxidative brain damage + +\nMitochondrial dysfunction + +\nCholinergic dysfunction + +\nImpaired neuronal glucose metabolism + +"}