| 1. |
- Darreh-Shori, T, et al.
(författare)
-
The apolipoprotein E varepsilon4 allele plays pathological roles in AD through high protein expression and interaction with butyrylcholinesterase.
- 2011
-
Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 32:7, s. 1236-48
-
Tidskriftsartikel (refereegranskat)abstract
- The apolipoprotein E (ApoE) varepsilon4 allele has consistently been established as an Alzheimer's disease (AD) risk factor, but its pathological contribution to AD is obscure. Certain butyrylcholinesterase (BuChE) polymorphisms together with the ApoE varepsilon4 allele synergistically increase the risk of AD. In addition, AD risk factors, i.e. advanced age, female gender and ApoE varepsilon4 are associated with different levels of CSF BuChE in AD patients, and BuChE protein attenuates Abeta fibrillization in vitro. Here we investigated the roles of ApoE and BuChE gene products as modulators of pathological features of AD in vivo. We found that AD risk factors were associated with different levels of ApoE protein in the CSF of AD patients (n=115). Women and ApoE varepsilon4 carriers had the highest levels of ApoE protein (up by 50-120%, p<0.01-0.0001), which were increased with age (r=0.30, p<0.0006). The CSF surrogate markers of pathological features of AD, i.e. high tau and P-tau, low Abeta(42) and high tau/Abeta(42) ratio, were associated with high levels of ApoE protein. Intriguingly, high ApoE protein levels were not only associated with low amounts of BuChE, but they also altered the aging and activity of this enzyme in concentration- and isoform-dependent manners, particularly in the presence of Abeta peptides. Both ApoE and BuChE levels were also differentially related to levels of the proinflammatory cytokine IL-1beta. In conclusion, ApoE varepsilon4 might impart its pathological role through high protein expression and interaction with BuChE, which in turn might modulate central cholinergic activity and Abeta load in the brain.
|
|
| 2. |
- Mardirossian, G, et al.
(författare)
-
A new rectal model for dosimetry applications
- 1999
-
Ingår i: Journal of Nuclear Medicine. - 0161-5505. ; 40:9, s. 1524-1531
-
Tidskriftsartikel (refereegranskat)abstract
- A revised geometric representative model of the lower part of the colon, including the rectum, the urinary bladder and prostate, is proposed for use in the calculation of absorbed dose from injected radiopharmaceuticals. The lower segment of the sigmoid colon as described in the 1987 Oak Ridge National Laboratory mathematical phantoms does not accurately represent the combined urinary bladder/rectal/prostate geometry. In the revised model in this study, the lower part of the abdomen includes an explicitly defined rectum. The shape of sigmoid colon is more anatomically structured, and the diameters of the descending colon are modified to better approximate their true anatomic dimensions. To avoid organ overlap and for more accurate representation of the urinary bladder and the prostate gland (in the male), these organs are shifted from their originally defined positions. The insertion of the rectum and the shifting of the urinary bladder will not overlap with or displace the female phantom's ovaries or the uterus. In the adult male phantom, the prostatic urethra and seminal duct are also included explicitly in the model. The relevant structures are defined for the newborn and 1-, 5-, 10- and 15-y-old (adult female) and adult male phantoms. METHODS: Values of the specific absorbed fractions and radionuclide S values were calculated with the SIMDOS dosimetry package. Results for 99mTc and other radionuclides are compared with previously reported values. RESULTS: The new model was used to calculate S values that may be crucial to calculations of the effective dose equivalent. For 131I, the S (prostate<--urinary bladder contents) and S (lower large intestine [LLI] wall<--urinary bladder contents) are 6.7 x 10(-6) and 3.41 x 10(-6) mGy/MBq x s, respectively. Corresponding values given by the MIRDOSE3 computer program are 6.23 x 10(-6) and 1.53 x 10(-6) mGy/MBq x s, respectively. The value of S (rectum wall<--urinary bladder contents) is 4.84 x 10(-5) mGy/MBq x s. For 99mTc, we report S (testes<--prostate) and S (LLI wall<--prostate) of 9.41 x 10(-7) and 1.53 x 10(-7) mGy/MBq x s versus 1.33 x 10(-6) and 7.57 x 10(-6) mGy/MBq x s given by MIRDOSE3, respectively. The value of S (rectum wall<--prostate) for 99mTc is given as 4.05 x 10(-6) mGy/MBq x s in the present model. CONCLUSION: The new revised rectal model describes an anatomically realistic lower abdomen region, thus giving improved estimates of absorbed dose. Due to shifting the prostate gland, a 30%-45% reduction in the testes dose and the insertion of the rectum leads to 48%-55% increase in the LLI wall dose when the prostate is the source organ.
|
|
