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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

Stereotyped pattern of spread of hypoperfusion in AD. The arrows in this diagram indicate the progression of hypoperfusion, starting from the precuneus, well before the onset of dementia, and spreading to the rest of the parietal cortex and the cingulate gyrus, then the frontal and temporal cortex, largely sparing the occipital cortex until late disease
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Fig4: Stereotyped pattern of spread of hypoperfusion in AD. The arrows in this diagram indicate the progression of hypoperfusion, starting from the precuneus, well before the onset of dementia, and spreading to the rest of the parietal cortex and the cingulate gyrus, then the frontal and temporal cortex, largely sparing the occipital cortex until late disease

Mentions: Cerebral hypoperfusion is demonstrable several years before the onset of clinical AD. Imaging studies in people with MCI [6, 18, 34], healthy carriers of the APOE ϵ4 allele [89] and those with gene mutations known to cause autosomal dominant AD [15] have shown that the distribution and spread of the hypoperfusion are highly stereotyped, and mirror the accumulation of Aβ amyloid within the brain parenchyma, particularly during the preclinical phases of disease. The first affected region is the precuneus, about 10 years before the development of dementia (Fig. 4). From there the hypoperfusion spreads to involve the cingulate gyrus and the lateral part of the parietal lobe, then the frontal and temporal lobes and eventually most of the cerebrum.Fig. 4


Cerebrovascular disease in ageing and Alzheimer's disease.

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

Stereotyped pattern of spread of hypoperfusion in AD. The arrows in this diagram indicate the progression of hypoperfusion, starting from the precuneus, well before the onset of dementia, and spreading to the rest of the parietal cortex and the cingulate gyrus, then the frontal and temporal cortex, largely sparing the occipital cortex until late disease
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig4: Stereotyped pattern of spread of hypoperfusion in AD. The arrows in this diagram indicate the progression of hypoperfusion, starting from the precuneus, well before the onset of dementia, and spreading to the rest of the parietal cortex and the cingulate gyrus, then the frontal and temporal cortex, largely sparing the occipital cortex until late disease
Mentions: Cerebral hypoperfusion is demonstrable several years before the onset of clinical AD. Imaging studies in people with MCI [6, 18, 34], healthy carriers of the APOE ϵ4 allele [89] and those with gene mutations known to cause autosomal dominant AD [15] have shown that the distribution and spread of the hypoperfusion are highly stereotyped, and mirror the accumulation of Aβ amyloid within the brain parenchyma, particularly during the preclinical phases of disease. The first affected region is the precuneus, about 10 years before the development of dementia (Fig. 4). From there the hypoperfusion spreads to involve the cingulate gyrus and the lateral part of the parietal lobe, then the frontal and temporal lobes and eventually most of the cerebrum.Fig. 4

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