Angiofensin converting enzyme density is increased in temporal cortex from patients with Alzheimer's disease

doi:10.1016/0014-2999(91)90584-D

European Journal of Pharmacology

Volume 200, Issues 2–3, 6 August 1991, Pages 289-292

https://doi.org/10.1016/0014-2999(91)90584-D Get rights and content

Abstract

The present study assesses the binding density of the selective angiotensin converting enzyme (ACE) radioligand [³H]ceranapril in brain tissue homogenates derived from patients with Alzheimer's disease and those from age-, sex- and post-mortem delay-matched neurologically normal patients. Saturation studies with [³H]ceranapril identified that the specific binding (defined by captopril, 10 μM) was homogenous and of high affinity. ACE inhibitor recognition site density was higher by some 70% in the temporal cortex (Brodmann area 22) from Alzheimer's patients whereas densities were similar in frontal cortex and cerebellum when compared to control tissue. It is unknown whether this apparently selective alteration in ACE density is directly related to. or a compensatory effect of the disease, but it provides additional support for the development of compounds which interact with the central angiotensin system as novel therapies for cognitive dysfunction.

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Citation Excerpt :
The permeability of the blood brain barrier (BBB) could increase by factors such as age, hypertension, sustained disease,including advanced AD (Starr et al., 2009), and the systemic ACE may enter the central RAS through the BBB, and brain ACE may increase the ACE level in peripheral blood by entering into the blood circulation (Akatsu et al., 2011). Moreover, ACE was shown to increase in AD brain (Arregui et al., 1982; Barnes et al., 1991; Miners et al., 2008; Miners et al. 2009; Savaskan et al., 2001), and it may correlated with the stage of disease (Miners et al. 2009). Meanwhile, our present study showed that serum ACE activity in AD patients was significantly higher than non-AD subjects, and the latter was associated with the severity of the development of AD.
To determine serum activities of angiotensin-converting enzyme (ACE) as a marker in diagnosis and determine the severity of Alzheimer's disease (AD),
We measured serum ACE activities in 59 moderate-severe AD, 19 mild AD, 45 amnestic mild cognitive impairment (aMCI) and 39 controls.
We found that patients in moderate-severe AD stages showed significantly higher ACE in comparison to aMCI and controls (ANOVA, LSD post hoc test: p: 0.02 and p: 0.01, respectively). Logistic regression analysis showed that if ACE activities added 200 U/L, the superiority of AD risk was 1.18 times higher than before compared with the control group (OR 1.18, 95% CI 1.01–1.74; P=0.49). By means of multivariate linear regression analysis, we found that age (β coefficient: 7.77; P: 0.01) was significantly associated with ACE activities. However, ACE activities were found to be significantly negatively associated with measures of orientation and immediate recall among the AD patients (r<0, P<0.05), whereas ACE activities were not associated with any MMSE scores among the non-AD groups (P > 0.05).uuuu
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^∗: Present address: Department of Pharmacology, The Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.

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Angiofensin converting enzyme density is increased in temporal cortex from patients with Alzheimer's disease

Abstract

Brain Res.

Brain Res.

Brain Res. Bull.

Anal. Biochem.

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

Neurosci. Lett.

Brain Res.

Brain Res.

Angiotensin converting enzyme in Alzheimer's disease: Increased activity in caudate nucleus and cortical areas

J. Neurochem.

ACE inhibition and cognition

Characterisation of [3H]ceranapril recognition sites in rat and human brain tissue

Neuropharmacology

Characterisation of [³H]ceranapril recognition sites in rat and human brain tissue