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Cerebrovascular disease in ageing and Alzheimer's disease.

Love S, Miners JS - Acta Neuropathol. (2015)

Bottom Line: Whilst demand for oxygen and glucose falls in late disease, functional MRI, near infrared spectroscopy to measure the saturation of haemoglobin by oxygen, and biochemical analysis of myelin proteins with differential susceptibility to reduced oxygenation have all shown that the reduction in blood flow in AD is primarily a problem of inadequate blood supply, not reduced metabolic demand.Whilst there is clearly an additive component to the clinical and pathological effects of hypoperfusion and AD, experimental and clinical observations suggest that the disease processes also interact mechanistically at a cellular level in a manner that exacerbates both.The elucidation of some of the mechanisms responsible for hypoperfusion in AD and for the interactions between CVD and AD has led to the identification of several novel therapeutic approaches that have the potential to ameliorate ischaemic damage and slow the progression of neurodegenerative disease.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Neurosciences, School of Clinical Sciences, Learning and Research Level 2, Southmead Hospital, University of Bristol, Bristol, BS10 5NB, UK. seth.love@bris.ac.uk.

ABSTRACT
Cerebrovascular disease (CVD) and Alzheimer's disease (AD) have more in common than their association with ageing. They share risk factors and overlap neuropathologically. Most patients with AD have Aβ amyloid angiopathy and degenerative changes affecting capillaries, and many have ischaemic parenchymal abnormalities. Structural vascular disease contributes to the ischaemic abnormalities in some patients with AD. However, the stereotyped progression of hypoperfusion in this disease, affecting first the precuneus and cingulate gyrus, then the frontal and temporal cortex and lastly the occipital cortex, suggests that other factors are more important, particularly in early disease. Whilst demand for oxygen and glucose falls in late disease, functional MRI, near infrared spectroscopy to measure the saturation of haemoglobin by oxygen, and biochemical analysis of myelin proteins with differential susceptibility to reduced oxygenation have all shown that the reduction in blood flow in AD is primarily a problem of inadequate blood supply, not reduced metabolic demand. Increasing evidence points to non-structural vascular dysfunction rather than structural abnormalities of vessel walls as the main cause of cerebral hypoperfusion in AD. Several mediators are probably responsible. One that is emerging as a major contributor is the vasoconstrictor endothelin-1 (EDN1). Whilst there is clearly an additive component to the clinical and pathological effects of hypoperfusion and AD, experimental and clinical observations suggest that the disease processes also interact mechanistically at a cellular level in a manner that exacerbates both. The elucidation of some of the mechanisms responsible for hypoperfusion in AD and for the interactions between CVD and AD has led to the identification of several novel therapeutic approaches that have the potential to ameliorate ischaemic damage and slow the progression of neurodegenerative disease.

No MeSH data available.


Related in: MedlinePlus

Microhaemorrhage associated with Aβ amyloid angiopathy. a Accumulation of numerous haemosiderin-laden macrophages around a cortical arteriole with a strongly eosinophilic wall. b The arteriole is immunopositive for Aβ, as demonstrated in this adjacent section. Bar 500 μm
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Fig3: Microhaemorrhage associated with Aβ amyloid angiopathy. a Accumulation of numerous haemosiderin-laden macrophages around a cortical arteriole with a strongly eosinophilic wall. b The arteriole is immunopositive for Aβ, as demonstrated in this adjacent section. Bar 500 μm

Mentions: Numerous studies have documented that patients with Aβ amyloid angiopathy are prone to cerebral haemorrhage, particularly lobar haemorrhage and cortical microhaemorrhage (Fig. 3) [43, 50, 51, 97, 111, 115, 131, 161, 171]. Both the ε2 and ε4 alleles of APOE increase the risk of Aβ amyloid angiopathy-associated lobar haemorrhage [52, 53, 116]; ε4 may do so by promoting the accumulation of Aβ in the walls of arterioles, and ε2 by promoting the development of vasculopathic changes, particularly fibrinoid necrosis, in the amyloid-laden vessels [54, 103]. Patients with Aβ amyloid angiopathy are also prone to develop superficial cortical siderosis [29, 93].Fig. 3


Cerebrovascular disease in ageing and Alzheimer's disease.

Love S, Miners JS - Acta Neuropathol. (2015)

Microhaemorrhage associated with Aβ amyloid angiopathy. a Accumulation of numerous haemosiderin-laden macrophages around a cortical arteriole with a strongly eosinophilic wall. b The arteriole is immunopositive for Aβ, as demonstrated in this adjacent section. Bar 500 μm
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835514&req=5

Fig3: Microhaemorrhage associated with Aβ amyloid angiopathy. a Accumulation of numerous haemosiderin-laden macrophages around a cortical arteriole with a strongly eosinophilic wall. b The arteriole is immunopositive for Aβ, as demonstrated in this adjacent section. Bar 500 μm
Mentions: Numerous studies have documented that patients with Aβ amyloid angiopathy are prone to cerebral haemorrhage, particularly lobar haemorrhage and cortical microhaemorrhage (Fig. 3) [43, 50, 51, 97, 111, 115, 131, 161, 171]. Both the ε2 and ε4 alleles of APOE increase the risk of Aβ amyloid angiopathy-associated lobar haemorrhage [52, 53, 116]; ε4 may do so by promoting the accumulation of Aβ in the walls of arterioles, and ε2 by promoting the development of vasculopathic changes, particularly fibrinoid necrosis, in the amyloid-laden vessels [54, 103]. Patients with Aβ amyloid angiopathy are also prone to develop superficial cortical siderosis [29, 93].Fig. 3

Bottom Line: Whilst demand for oxygen and glucose falls in late disease, functional MRI, near infrared spectroscopy to measure the saturation of haemoglobin by oxygen, and biochemical analysis of myelin proteins with differential susceptibility to reduced oxygenation have all shown that the reduction in blood flow in AD is primarily a problem of inadequate blood supply, not reduced metabolic demand.Whilst there is clearly an additive component to the clinical and pathological effects of hypoperfusion and AD, experimental and clinical observations suggest that the disease processes also interact mechanistically at a cellular level in a manner that exacerbates both.The elucidation of some of the mechanisms responsible for hypoperfusion in AD and for the interactions between CVD and AD has led to the identification of several novel therapeutic approaches that have the potential to ameliorate ischaemic damage and slow the progression of neurodegenerative disease.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Neurosciences, School of Clinical Sciences, Learning and Research Level 2, Southmead Hospital, University of Bristol, Bristol, BS10 5NB, UK. seth.love@bris.ac.uk.

ABSTRACT
Cerebrovascular disease (CVD) and Alzheimer's disease (AD) have more in common than their association with ageing. They share risk factors and overlap neuropathologically. Most patients with AD have Aβ amyloid angiopathy and degenerative changes affecting capillaries, and many have ischaemic parenchymal abnormalities. Structural vascular disease contributes to the ischaemic abnormalities in some patients with AD. However, the stereotyped progression of hypoperfusion in this disease, affecting first the precuneus and cingulate gyrus, then the frontal and temporal cortex and lastly the occipital cortex, suggests that other factors are more important, particularly in early disease. Whilst demand for oxygen and glucose falls in late disease, functional MRI, near infrared spectroscopy to measure the saturation of haemoglobin by oxygen, and biochemical analysis of myelin proteins with differential susceptibility to reduced oxygenation have all shown that the reduction in blood flow in AD is primarily a problem of inadequate blood supply, not reduced metabolic demand. Increasing evidence points to non-structural vascular dysfunction rather than structural abnormalities of vessel walls as the main cause of cerebral hypoperfusion in AD. Several mediators are probably responsible. One that is emerging as a major contributor is the vasoconstrictor endothelin-1 (EDN1). Whilst there is clearly an additive component to the clinical and pathological effects of hypoperfusion and AD, experimental and clinical observations suggest that the disease processes also interact mechanistically at a cellular level in a manner that exacerbates both. The elucidation of some of the mechanisms responsible for hypoperfusion in AD and for the interactions between CVD and AD has led to the identification of several novel therapeutic approaches that have the potential to ameliorate ischaemic damage and slow the progression of neurodegenerative disease.

No MeSH data available.


Related in: MedlinePlus