Structural Changes in Alzheimers Disease Brain Microvessels

Christov, Alexander; Ottman, J. Todd; Hamdheydari, L.; Grammas, Paula

doi:10.2174/156720508785132334

Cited by 42 publications

(38 citation statements)

References 37 publications

(54 reference statements)

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“…Vessels under 50 lm in diameter from AD patients show a decrease in the amount of collagen IV, compared with aged-matched controls (Christov et al, 2008). Heparan sulfate proteoglycans such as fibronectin and perlecan provide stability and flexibility to the basement membrane, accelerating the aggregation of Ab by high-affinity interactions (Castillo et al, 1997;Cotman et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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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“…Decreased amounts of collagen IV have been reported in small diameter vessels (<50 μm) from AD patients compared to aged-matched controls (Christov et al, 2008). Conversely, the levels of HSPGs were increased in AD brains (Berzin et al, 2000; Shimizu et al, 2009).…”

Section: Role Of Cvbm and Perivascular Drainage In Caamentioning

confidence: 99%

The Cerebrovascular Basement Membrane: Role in the Clearance of Î²-amyloid and Cerebral Amyloid Angiopathy

Morris

Carare

Schreiber

et al. 2014

Front. Aging Neurosci.

103

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Cerebral amyloid angiopathy (CAA), the accumulation of β-amyloid (Aβ) peptides in the walls of cerebral blood vessels, is observed in the majority of Alzheimer’s disease (AD) brains and is thought to be due to a failure of the aging brain to clear Aβ. Perivascular drainage of Aβ along cerebrovascular basement membranes (CVBMs) is one of the mechanisms by which Aβ is removed from the brain. CVBMs are specialized sheets of extracellular matrix that provide structural and functional support for cerebral blood vessels. Changes in CVBM composition and structure are observed in the aged and AD brain and may contribute to the development and progression of CAA. This review summarizes the properties of the CVBM, its role in mediating clearance of interstitial fluids and solutes from the brain, and evidence supporting a role for CVBM in the etiology of CAA.

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“…In AD brain, substantial morphological and functional cerebrovascular abnormalities were observed including, microvasculature irregularities and atrophy, basement membrane disruption and deposition of heparin sulfate proteoglycans, collagen IV and laminin, decreased cerebrovascular network density, endothelial cell alteration i.e., increased pinocytosis, decreased levels of mitochondria and detection of elevated endothelial cell markers VCAM-1 and E-selectin (Kalaria and Pax, 1995; Farkas and Luiten, 2001; Bailey et al, 2004; Christov et al, 2008; Zuliani et al, 2008). These vascular alterations are referred to as CAA, which associates with ischemic lesions, micro- and macro-hemorrhages, and impaired cerebral blood flow.…”

Section: Vascular Pathology In Admentioning

confidence: 99%

Role of amyloid peptides in vascular dysfunction and platelet dysregulation in Alzheimerâ€™s disease

Canobbio

Abubaker

Visconte

et al. 2015

Front. Cell. Neurosci.

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Alzheimer’s disease (AD) is the most common neurodegenerative cause of dementia in the elderly. AD is accompanied by the accumulation of amyloid peptides in the brain parenchyma and in the cerebral vessels. The sporadic form of AD accounts for about 95% of all cases. It is characterized by a late onset, typically after the age of 65, with a complex and still poorly understood aetiology. Several observations point towards a central role of cerebrovascular dysfunction in the onset of sporadic AD (SAD). According to the “vascular hypothesis”, AD may be initiated by vascular dysfunctions that precede and promote the neurodegenerative process. In accordance to this, AD patients show increased hemorrhagic or ischemic stroke risks. It is now clear that multiple bidirectional connections exist between AD and cerebrovascular disease, and in this new scenario, the effect of amyloid peptides on vascular cells and blood platelets appear to be central to AD. In this review, we analyze the effect of amyloid peptides on vascular function and platelet activation and its contribution to the cerebrovascular pathology associated with AD and the progression of this disease.

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Structural Changes in Alzheimers Disease Brain Microvessels

Cited by 42 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

The Cerebrovascular Basement Membrane: Role in the Clearance of Î²-amyloid and Cerebral Amyloid Angiopathy

Role of amyloid peptides in vascular dysfunction and platelet dysregulation in Alzheimerâ€™s disease

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