Dysregulation of ACE-1 in Normal Aging and the Early Stages of Alzheimer’s Disease

Figures

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  Figure 1.. ACE-1 and Ang-II protein levels are elevated in relation to normal aging in the frontal and temporal cortex. (A–D) Scatterplots showing a positive correlation between ACE-1 protein concentration and age in the frontal cortex (FCx―n = 84; r = 0.362, p = .0006) and temporal cortex (TCx―n = 84; r = 0.408, p = .0001). ACE-1 protein was elevated in those aged 65 years and older compared to those aged ≤45 years in the FCx (≤45 years n = 18, 46–65 years n = 35, >65 years n = 31; p = .012) and TCx (≤45 years n = 18, 46–65 years n = 35, >65 years n = 31; p = .039). (E–H) Scatterplots showing a positive correlation between Ang-II concentration normalized to the total protein and age (FCx—n = 84; r = 0.530, p < .0001 and TCx— n = 84; r = 0.559, p < .0001). A significant increase in Ang-II concentration in those aged 65 years and above was observed across both regions (FCx―≤45 years n = 18, 46–65 years n = 35, >65 years n = 31; ≤45 years vs >65 years p < .0001, 46–65 years vs >65 years p = .0057 and TCx―≤45 years n = 18, 46–65 years n = 35, >65 years n = 31; ≤45 years vs >65 years p < .0001, 46–65 years vs >65 years p < .0001). (I–L) Scatterplots showing an inverse correlation between ACE-1…

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  Figure 2.. ACE-1 protein level is positively correlated, and ACE-1 enzyme activity is negatively correlated, with Ang-II in normal aging. (A and C) Scatterplots showing a positive correlation between ACE-1 protein level and Ang-II concentration in the frontal cortex (FCx―n = 87; r = 0.290, p = .0065) and temporal cortex (TCx―n = 85; r = 0.452, p < .0001). (B and D) Scatterplots showing an inverse correlation between ACE-1 enzyme activity and Ang-II concentration in both regions (FCx—n = 87; r = −0.391, p = .0002 and TCx—n = 84; r = −0.278, p = .011). ACE-1 activity is expressed as relative fluorescence units (r.f.u). Linear regression lines of best fit and 95% confidence intervals are shown. ACE-1 = angiotensin-converting enzyme-1; Ang-II = angiotensin-II.

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  Figure 3.. The ratio of ACE-1:ACE-2 protein concentration is increased with normal aging in contrast to enzyme activity. (A–D) Scatterplots showing a positive correlation between the ratio of ACE-1:ACE-2 protein concentration and age in the frontal cortex (FCx―n = 87; r = 0.356, p = .0007) and temporal cortex (TCx―n = 86; r = 0.358, p = .0007). The ratio of ACE-1:ACE-2 protein concentration was significantly elevated in those aged >65 years and older compared to ≤45 years in the FCx (≤45 years n = 18, 46–65 years n = 35, >65 years n = 34; p = .0073). No change was observed in the TCx (≤45 years n = 20, 46–65 years n = 35, >65 years n = 31). (E–H) Scatterplots showing an inverse correlation between the ACE-1:ACE-2 enzyme activity ratio and age (n = 69; r = −0.587, p < .0001) and a reduction in the ACE-1:ACE-2 enzyme activity ratio in the 65 years and older age group in the FCx (≤45 years n = 14, 46–65 years n = 26, >65 years n = 30; ≤45 years vs >65 years p = .0009, 45–65 years vs >65 years p = .0023). No differences were observed in the TCx. Linear regression line of best fit and 95% confidence intervals and medians with 95% confidence intervals are shown. **p < .01 and ***p < .001. ACE-1 =…

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  Figure 4.. ACE-1 enzyme activity is increased in the early stages of Alzheimer’s disease (AD). (A–D) Scatterplots showing ACE-1 protein level is unchanged between AD and age-matched controls (control = 27, AD = 39), and in relation to Braak tangle stage (BS 0–II = 18, BS III–IV = 18, BS V–VI = 19), in the frontal cortex (FCx) and temporal cortex (TCx). (E–H) Scatterplots showing no change in Ang-II concentration, normalized to the total protein, between AD and age-matched controls (control = 27, AD = 39) and Braak tangle stage in the FCx and TCx. (I–L) Scatterplots showing no significant differences in ACE-1 activity between control and AD cases (control = 27, AD = 39) and BS (BS 0–II = 18, BS III–IV = 18, BS V–VI = 19) in the FCx and a significant increase in ACE-1 activity in AD compared to age-matched controls (control = 27, AD = 38; p = .028) and in BS III–IV compared to BS 0–II (BS 0–II = 19, BS III–IV = 20, BS V–VI = 18; p = .01) in the TCx. ACE-1 activity is expressed as relative fluorescence units (r.f.u). Standard error of the mean is shown. *p < .05. ACE-1 = angiotensin-converting enzyme-1; Ang-II = angiotensin-II.

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  Figure 5.. The ratio of ACE-1:ACE-2 enzyme activity is increased in Alzheimer’s disease (AD). (A–D) Scatterplots showing no change in ratio of ACE-1:ACE-2 protein concentration in relation to AD (control = 30, AD = 39) and Braak tangle stage (BS 0–II = 20, BS III–IV = 19, BS V–VI = 20) in the frontal cortex (FCx) and temporal cortex (TCx). (E–H) Scatterplots showing an increase in the ratio of ACE-1:ACE-2 enzyme activity between AD and controls (control = 26, AD = 30; p = .036) and a trend towards a higher ratio in relation to Braak stage (BS 0–II = 19, BS III–IV = 14, BS V–VI = 16) in the FCx. No change observed between AD and controls and BS in the TCx. Median and 95% confidence intervals are shown. *p < .05. ACE-1 = angiotensin-converting enzyme-1; ACE-2 = angiotensin-converting enzyme-2.