Can disturbed brain microcirculation cause Alzheimer’s disease?

Jc, de la Torre; Mussivand, Tofy

doi:10.1080/01616412.1993.11740127

Cited by 318 publications

(187 citation statements)

References 64 publications

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“…Considering vascular changes in the brain in diabetes, it is known that structural abnormalities at the microvascular level include thickening of capillary basement membranes and decreased capillary density [21]. During ageing, brain capillaries undergo progressive degeneration, as evidenced by amyloid deposition, thickened basement membranes and reduced vessel elasticity [22,23]. Considering the similarities of these events, it is possible that diabetes and ageing share the same pathogenic processes.…”

Section: Discussionmentioning

confidence: 99%

Voxel-based morphometry demonstrates reduced grey matter density on brain MRI in patients with diabetic retinopathy

et al. 2006

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Aims/hypothesis: In addition to nephropathy, retinopathy and peripheral neuropathy, a microvascular complication of type 1 diabetes that may be tentatively referred to as 'diabetic encephalopathy' has gained increasing attention. There is growing evidence that lowered cognitive performance in patients with type 1 diabetes is related to chronic hyperglycaemia rather than recurrent episodes of severe hypoglycaemia, as previously speculated. The aim of our study was to use magnetic resonance imaging (MRI) to establish whether long-term hyperglycaemia, resulting in advanced retinopathy, contributes to structural changes in the brain (reduced grey matter). Subjects, materials and methods: We applied voxel-based morphometry on magnetic resonance images to compare grey matter density (GMD) between three groups of participants. GMD is used as a marker of cortical atrophy. We compared 13 type 1 diabetic patients with a microvascular complication (i.e. proliferative retinopathy) with 18 type 1 diabetic patients who did not have retinopathy in order to assess the effects of microvascular changes on GMD. Both patient groups were compared with 21 healthy control subjects to assess the effect of diabetes in itself. Results: Patients with diabetic retinopathy showed reduced GMD in the right inferior frontal gyrus and right occipital lobe compared both with patients without retinopathy and with healthy controls (p<0.05). Conclusions/interpretation: Our data show that patients with type 1 diabetes, who, as a consequence of chronic hyperglycaemia, had developed advanced retinopathy, also showed increased focal cortical atrophy on brain MRI.

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Section: Discussionmentioning

confidence: 99%

Voxel-based morphometry demonstrates reduced grey matter density on brain MRI in patients with diabetic retinopathy

et al. 2006

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“…They also considered the effects of dietary supplements as a tool to treat states of PUFA imbalance, but they did not include aging in their review. However, structural changes in the blood-brain barrier complex, in aging and in Alzheimer patients, were reported [28,45]. Despite the knowledge about structural changes, the knowledge about functional changes is quite limited.…”

Section: Blood-brain Barriermentioning

confidence: 99%

The role of polyunsaturated fatty acids in restoring the aging neuronal membrane

Yehuda¹,

Rabinovitz²,

Carasso³

et al. 2002

Neurobiology of Aging

348

200

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In addition to a gradual loss of neurons in various brain regions, major biochemical changes in the brain affect the neuronal membrane that is the "site of action" for many essential functions including long-term potentiation (LTP), learning and memory, sleep, pain threshold, and thermoregulation. Normal physiological functioning includes the transmission of axonal information, regulation of membrane-bound enzymes, control of ionic channels and various receptors. All are highly dependent on membrane fluidity, where rigidity is increased during aging. The significantly higher level of cholesterol in aging neuronal membrane, the slow rate of cholesterol turnover, and the decreased level of total polyunsaturated fatty acids (PUFA) may result from poor passage rate via the blood-brain barrier, or from a decreased rate of incorporation into the membrane, or a decrease in the activities of delta-6 and delta-9 desaturase enzymes. The added oxidative stress, which leads to an increase of free radicals leading to a decrease in membrane fluidity, may respond to a restricted diet, and thereby overcome the damaging effects of the free radicals. A central focus of this review is that a specific ratio of n-3/n-6 PUFA can restore many of these age-related effects.

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“…8). Reduced blood flow has been reported as one of the most consistent physiological deficits in AD (9,10); however, it remains unclear whether the reduced cerebral blood flow is a response to neuronal damage or a factor initiating the characteristic neuropathology. In vivo studies showed the effect of A␤ on cerebral blood flow and vessel architecture in a mouse model for AD (11,12).…”

mentioning

confidence: 99%

Altered morphology and 3D architecture of brain vasculature in a mouse model for Alzheimer's disease

Meyer

Ulmann-Schuler

Staufenbiel

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

232

215

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Substantial evidence from epidemiological, pathological, and clinical reports suggests that vascular factors are critical in the pathogenesis of Alzheimer's disease (AD), and changes in blood flow are currently the most reliable indicators of the disease. We previously reported that older APP23 transgenic (tg) mice have significant blood flow alterations correlated with structural modifications of blood vessels. For the present study, our objective was to analyze the age-dependent morphological and architectural changes of the cerebral vasculature of APP23 tg mice. To visualize the 3D arrangement of the entire brain vasculature, we used vascular corrosion casts. Already at young ages, when typically parenchymal amyloid plaques are not yet present, APP23 tg mice had significant alterations, particularly of the microvasculature, often accompanied by small deposits attached to the vessels. In older animals, vasculature abruptly ended at amyloid plaques, resulting in holes. Often, small deposits were sitting near or at the end of truncated vessels. Between such holes, the surrounding vascular array appeared more dense and showed features typical for angiogenesis. We propose that small amyloid aggregates associated with the microvasculature lead to morphological and architectural alterations of the vasculature, resulting in altered local blood flow. The characteristic early onset of vascular alterations suggests that imaging blood flow and/or vasculature architecture could be used as a tool for early diagnosis of the disease and to monitor therapies. amyloid precursor protein ͉ cerebral blood flow ͉ scanning electron microscopy ͉ vascular corrosion casting T he typical clinical picture of Alzheimer's disease (AD) includes a progressive decline of memory function, often accompanied by other clinical signs such as agitation, aggression, sleep disturbances, and social withdrawal. Nonetheless, brain autopsy is needed to positively confirm the diagnosis (1). A high density of neuritic plaques, neurofibrillary tangles, and vascular amyloid (A␤) is a characteristic neuropathological marker of AD (2, 3). Plaques and tangles in the neuropil may affect neuronal function and also contribute to the neuronal damage; however, it is unclear whether their incidence correlates with the clinical signs and symptoms of cognitive impairment characteristic of the disease (4). Evidence suggests that cerebrovascular pathologies, such as structural alterations (5), atherosclerotic lesions (6), and impaired hemodynamic responses (7), are early features of AD (for review, see ref. 8). Reduced blood flow has been reported as one of the most consistent physiological deficits in AD (9, 10); however, it remains unclear whether the reduced cerebral blood flow is a response to neuronal damage or a factor initiating the characteristic neuropathology. In vivo studies showed the effect of A␤ on cerebral blood flow and vessel architecture in a mouse model for AD (11,12). In other models, cerebrovascular regulatory mechanisms, such as endothelium-depende...

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Can disturbed brain microcirculation cause Alzheimer’s disease?

Cited by 318 publications

References 64 publications

Voxel-based morphometry demonstrates reduced grey matter density on brain MRI in patients with diabetic retinopathy

Voxel-based morphometry demonstrates reduced grey matter density on brain MRI in patients with diabetic retinopathy

The role of polyunsaturated fatty acids in restoring the aging neuronal membrane

Altered morphology and 3D architecture of brain vasculature in a mouse model for Alzheimer's disease

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