- Email: [email protected]
Association between serum thyroid hormone and cerebral amyloidosis in cognitively diverse elderly
P648 P3-079
Poster Presentations: P3 TOXIC Ab CONFORMER IS PRESENT IN BRAINS AND CEREBROSPINAL FLUID OBTAINED FROM NONDEMENTED INDIVIDUALS
Yasushi Tomidokoro, Kazuhiro Ishii, Akira Tamaoka, University of Tsukuba, Tsukuba, Japan. Contact e-mail: [email protected] Background: Ab molecules harbor turn structure at Gly25-Ser26 or Glu22-Asp23. Ab with turn structure at Glu22-Asp23 is reported to be more toxic and specifically labeled with monoclonal 11A1 [Murakami K, et al., 2010]. Last year, we reported that toxic Ab conformer is present in Alzheimer disease (AD) brains but not in non-AD control brains where Ab is not accumulated, and that toxic Ab conformer is also found in cerebrospinal fluid (CSF) in elderly non-AD cases. Here we analyzed aged non-demented cases, and non-AD CSF with various ages including young individuals to find out if generation of toxic Ab conformer is the earliest event in pathological cascade of AD proceeding amyloid deposition or rather physiological phenomenon. Methods: Paraffin embedded sections obtained from autopsied nondemented control cases (ages of 73 to 82y) were immunnostained with 11A1. CSF obtained from 10 cases of control subjects (ages of 16 to 67y) were analyzed by a combination of immunoprecipitation and Western blotting analyses. Monoclonal 4G8 was used as a control. Results: Large number of amyloid plaques was visualized with 11A1 in AD sections. Some 11A1 positive plaques were found in aged control cases, where small numbers of 4G8-positive plaques were also present. Cases lacking amyloid plaques did not show any 11A1-positive plaques. In all the CSF samples analyzed, toxic Ab conformer was present including 2 cases of teen ager. Conclusions: Toxic Ab conformer is suggested to be present in amyloid plaques in aged non-demented individuals as well as in CSF obtained from young controls. It is necessary to increase the number of CSF examined to clarify if the amounts or proportion of toxic Ab conformer in CSF is associated with aging.
P3-080
ASSOCIATION BETWEEN SERUM THYROID HORMONE AND CEREBRAL AMYLOIDOSIS IN COGNITIVELY DIVERSE ELDERLY
Hyo Jung Choi1,2, Young Min Choe1,2, Min Soo Byun1,2, Bo Kyung Sohn3, Hyewon Baek2, Dahyun Yi4, Ji Young Han5, Jong Inn Woo2, Dong Young Lee1,2, 1Seoul National University College of Medicine, Seoul, South Korea; 2Seoul National University Hospital, Seoul, South Korea; 3 SMG-SNU Boramae Medical Center, Seoul, South Korea; 4Department of Neuropsychiatry, Seoul National University Hospital & Seoul National University College of Medicine, Seoul, South Korea; 5Department of Neuropsychiatry, Seoul National University Hospital, Seoul, South Korea. Contact e-mail: [email protected] Background: Cerebral amyloid-beta protein (Ab) deposition has been considered as a key initiating step in Alzheimer’s disease (AD) process. Although several preclinical studies have suggested the possible linkage between thyroid hormone and cerebral amyloidosis, the association between serum thyroid hormone and cerebral Ab deposition in human brain is still poorly known. We aimed to investigate the association in cognitively diverse elderly. Methods: Sixty two cognitively normal (CN), 29 amnestic mild cognitive impairment (aMCI) and 25 Alzheimer’s disease dementia (AD) elderly individuals were included. All participants received comprehensive clinical and neuropsychological assessment based on the CERAD protocol, 11C-labeled Pittsburgh
Compound B (PiB) positron emission tomography, volumetric MRI, and quantification for serum thyroid hormone including total T3, free T4 and TSH. Global cerebral Ab deposition was defined as mean cortical PiB retention of the cortical regions including frontal, lateral temporal, lateral parietal and precuneus/posterior cingulate cortices. Results: Univariate analyses showed significant positive association of global cerebral Ab deposition with the levels of serum total T3 in total participants. In subgroup analysis, such association was found only in cognitively normal (CN) subjects, but not in MCI and AD patients. Independent positive associations between the levels of serum total T3 and global cerebral Ab deposition in CN participants were still significant even after controlling the effect of age, gender, apolipoprotein E ε4 genotype. Moreover, high serum T3 levels were significantly associated with poor global cognitive function measured by the total score of the CERAD neuropsychological test battery in CN participants. No association was found between both free T4 and TSH, and cortical 11C-PiB retention. Conclusions: Our findings indicate the association between thyroid hormone in blood, especially total T3 level, and the degree of cerebral amyloidosis in cognitively healthy elderly people. The mechanism underlying the relationship between the two needs to be further investigated.
P3-081 Table 1 Comparisons of serum thyroid hormone CN (n¼62)
aMCI (n¼29)
AD (n¼25)
Test value
p value
T3(mg/dL) 121.7 6 16.7 117.8 615.5 125.8 617.5 F(2.113)¼ 1.580 0.211 FreeT4(mg/dL) 1.08 60.22 1.15 6 0.19 1.14 6 0.21 F(2.113)¼ 1.517 0.224 TSH (mg/dL) 1.82 60.92 2.53 62.19 1.82 61.15 F(2.113)¼ 2.917 0.058
Date are presented as means 6 SD and anatyzed with ANOVA with degrees of freedom presented with the F values in the table. SD: standard deviation.CN: cognitively normal,aMCI: mild cognitive impairment. AD: Alzheimer’sdementia
Table 2 Pearson correlation of serum thyroid hormones with cerebral amyloid burden
overall participants (n¼116)
CN (n¼62)
aMCI (n¼29)
AD (n¼25)
Serum T3(mg/dL) Serum FreeT4(mg/dL) Serum TSH(mg/dL) Serum T3(mg/dL) Serum FreeT4(mg/dL) Serum TSH(mg/dL) Serum T3(mg/dL) Serum FreeT4(mg/dL) Serum TSH(mg/dL) Serum T3(mg/dL) Serum FreeT4(mg/dL) Serum TSH(mg/dL) Serum T3(mg/dL)
r
p
0.234 0.073 -0.017 0.332 -0.091 -0.010 0.002 0.051 0.035 0.319 0.104 -0.233 0.319
0.011* 0.438 0.855 0.008* 0.481 0.936 0.993 0.793 0.856 0.120 0.620 0.261 0.120
CN ¼ cognitively normal elderly, aMCI ¼ amnestic mild cognitive impairment, AD ¼ Alzheimer’s disease dementia
Poster Presentations: P3 Table 3 Partial correlation of serum thyroid hormone with cerebral amyloid burden in CN
Serum T3(mg/dL) Serum FreeT4(mg/dL) Serum TSH(mg/dL)
r
P
0.365 -0.031 -0.040
0.004* 0.817 0.762
CN ¼ cognitively normal elderly, partial correlation of serum thyroid hormone with cerebral amyloid burden controlling age, gender and ApoE e4 genotype, df ¼ 57
Table 4 Results from multiple regression analyses in CN (n ¼ 62) Independent Dependent variable variable
B
SE
t
P
R2
F F(4,57) ¼ 2.913
Cerebral amyloid burden Age Gender ApoE ε4 genotype Serum T3 level
.005 -.005 .105 .004
.004 .043 .061 .001
1.241 -.108 1.720 2.962
.111
.220 .914 .091 .004 F(4,57) ¼ 0.638 -0.024
Cerebral amyloid burden Age Gender ApoE ε4 genotype Serum T4 level
.002 -.008 .098 -.027
.004 .498 .621 .050 -.154 .878 .069 1.398 .168 .118 -.232 .817 F(4,57) ¼ 0.648 -0.024
Cerebral amyloid burden Age Gender ApoE ε4 genotype Serum TSH level
.003 -.013 .101 -.008
.004 .596 .554 .046 -.274 .785 .066 1.540 .129 .027 -.304 .762
CN ¼cognitively normal elderly, B ¼ Regression coefficient, SE ¼ Standard error.
Table 5 Partial correlation of serum T3 with cognition in CN elderly
CERAD total scorel (TS1) CERAD total score2(TS2)
r
P
-0.312 -0.295
0.018* 0.026*
Partial correlation of serum T3 with cognition controlling age, gender and education, df ¼ 55
ASSOCIATIONS BETWEEN BDNF SERUM LEVELS AND ALZHEIMER’S DISEASE-RELATED MEASURES: THE FRAMINGHAM STUDY Galit Weinstein1, Sarah R. Preis2,3, Alexa S. Beiser2,3, Claudia L. Satizabal4,5, Nicole L. Spartano4, Tai C. Chen4, Vasan S. Ramachandran4,5, Sudha Seshadri4,5, 1University of Haifa, Haifa, Israel; 2Boston University School of Public Health, Boston, MA, USA; 3The Framingham Study, Framingham, MA, USA; 4Boston University School of Medicine, Boston, MA, USA; 5The Framingham Heart Study, Framingham, MA, USA. Contact e-mail: [email protected] Background: Brain derived neurotrophic factor (BDNF) may play a role in the pathogenesis of Alzheimer’s disease (AD) through neurotrophic effects on basal cholinergic neurons. We have previously
P649
shown that among cognitively intact individuals, reduced serum levels predict AD risk. Thus, we have now examined the association of various demographic, behavioral and clinical AD related measures with serum BDNF levels. Methods: BDNF was measured in 3,689 participants (mean age 65 years, 56% women) from the Framingham Study’s Original (n¼669) and Offspring (n¼3,020) cohorts. Linear regression was used to evaluate the cross-sectional relationship between AD related measures (waist-hip ratio, waist circumference, body mass index, systolic blood pressure, hypertension, hypertension treatment, current cigarette smoking, alcohol use, diabetes, total cholesterol, HDL cholesterol, statin use, history of CVD, history of atrial fibrillation, and APOE4) and BDNF. Presence of depressive symptoms, score on a physical activity index, total caloric intake, renal function (estimated glomerular function rate), and circulating levels of triglycerides, C-reactive protein, TNF-alpha and homocysteine were also assessed but only in the Offspring cohort. Results: Participants with serum BDNF levels at the bottom two quintiles compared to the rest were older (p¼0.03) and more likely to be males (p<0.001). Adjusting for age and sex, higher BDNF levels were observed among current smokers compared to former or never smokers (b[SE]¼2286 [427], p-value<0.0001), and to a lesser extent among persons who are physically active (b[SE]¼ 51.0[24.3], p-value¼0.04 for a unit elevation in physical activity index) and who have high total-cholesterol (b[SE]¼19.4[3.7], p-value<0.0001). In addition, BDNF levels were lower among persons with prevalent atrial fibrillation (b[SE]¼-1942.3[670.8], p-value¼0.004), and were negatively associated with circulating TNF-a levels (b[SE]¼-974 [358], p-value¼0.007). Conclusions: BDNF may be modulated by behavioral and clinical factors which, in turn, are associated with AD risk. Thus physical activity, atrial fibrillation and inflammation may increase AD risk partly through changes in BDNF levels. Conversely, higher BDNF levels in current smokers could partially explain prior conflicting reports on the association of current smoking with AD risk, serving to mitigate the expected adverse effects. Mediation analyses to further explore the possible role of BDNF in the AD causal pathway will be presented.
P3-082
COMPROMISED REGULATION OF SERUM CYTOKINE LEVELS AND BDNF DUE TO LOW LEVELS OF VITAMIN D IN PATIENTS WITH EARLY- OR LATE-ONSET ALZHEIMER’S DISEASE OR PARKINSON’S DISEASE
Duygu Gezen-Ak1, Bas¸ar Bilgic¸2, Has¸met Hanagası2, Sibel Ertan1, € ur S. Araz1, Ebba Lohmann2, Irem L. Atasoy1, Merve Alaylıoglu1, Om€ € 1, Ays¸eg€ul G€und€uz1, G€unes¸ Kızıltan2, H€ulya Apaydın1, Burak Onal Hakan I. Gurvit2, Selma Yılmazer1, Erdinc Dursun1, 1Istanbul University, Cerrahpasa Faculty of Medicine, Istanbul, Turkey; 2Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey. Contact e-mail: [email protected] Background: Neurodegenerative disorders like Alzheimer’s disease (AD), Parkinson’s disease (PD) were suggested to involve neuroinflammation as part of the pathogenesis. Interleukin-1-beta (IL-1b), interleukin-6 (IL-6), tumor-necrosis-factor-alpha (TNFa) are inflammatory cytokines contribute to neuroinflammation in these disorders. Brain derived neurotrophic factor (BDNF) participates in learning, memory, and behavior. Vitamin D is a seco-steroid hormone that has the capacity regulate immune response and neurotrophic factor synthesis. Methods: The circulating form of vitamin D in blood (25OHD) is measured in four patient groups including AD
Poster Presentations: P3 TOXIC Ab CONFORMER IS PRESENT IN BRAINS AND CEREBROSPINAL FLUID OBTAINED FROM NONDEMENTED INDIVIDUALS
Yasushi Tomidokoro, Kazuhiro Ishii, Akira Tamaoka, University of Tsukuba, Tsukuba, Japan. Contact e-mail: [email protected] Background: Ab molecules harbor turn structure at Gly25-Ser26 or Glu22-Asp23. Ab with turn structure at Glu22-Asp23 is reported to be more toxic and specifically labeled with monoclonal 11A1 [Murakami K, et al., 2010]. Last year, we reported that toxic Ab conformer is present in Alzheimer disease (AD) brains but not in non-AD control brains where Ab is not accumulated, and that toxic Ab conformer is also found in cerebrospinal fluid (CSF) in elderly non-AD cases. Here we analyzed aged non-demented cases, and non-AD CSF with various ages including young individuals to find out if generation of toxic Ab conformer is the earliest event in pathological cascade of AD proceeding amyloid deposition or rather physiological phenomenon. Methods: Paraffin embedded sections obtained from autopsied nondemented control cases (ages of 73 to 82y) were immunnostained with 11A1. CSF obtained from 10 cases of control subjects (ages of 16 to 67y) were analyzed by a combination of immunoprecipitation and Western blotting analyses. Monoclonal 4G8 was used as a control. Results: Large number of amyloid plaques was visualized with 11A1 in AD sections. Some 11A1 positive plaques were found in aged control cases, where small numbers of 4G8-positive plaques were also present. Cases lacking amyloid plaques did not show any 11A1-positive plaques. In all the CSF samples analyzed, toxic Ab conformer was present including 2 cases of teen ager. Conclusions: Toxic Ab conformer is suggested to be present in amyloid plaques in aged non-demented individuals as well as in CSF obtained from young controls. It is necessary to increase the number of CSF examined to clarify if the amounts or proportion of toxic Ab conformer in CSF is associated with aging.
P3-080
ASSOCIATION BETWEEN SERUM THYROID HORMONE AND CEREBRAL AMYLOIDOSIS IN COGNITIVELY DIVERSE ELDERLY
Hyo Jung Choi1,2, Young Min Choe1,2, Min Soo Byun1,2, Bo Kyung Sohn3, Hyewon Baek2, Dahyun Yi4, Ji Young Han5, Jong Inn Woo2, Dong Young Lee1,2, 1Seoul National University College of Medicine, Seoul, South Korea; 2Seoul National University Hospital, Seoul, South Korea; 3 SMG-SNU Boramae Medical Center, Seoul, South Korea; 4Department of Neuropsychiatry, Seoul National University Hospital & Seoul National University College of Medicine, Seoul, South Korea; 5Department of Neuropsychiatry, Seoul National University Hospital, Seoul, South Korea. Contact e-mail: [email protected] Background: Cerebral amyloid-beta protein (Ab) deposition has been considered as a key initiating step in Alzheimer’s disease (AD) process. Although several preclinical studies have suggested the possible linkage between thyroid hormone and cerebral amyloidosis, the association between serum thyroid hormone and cerebral Ab deposition in human brain is still poorly known. We aimed to investigate the association in cognitively diverse elderly. Methods: Sixty two cognitively normal (CN), 29 amnestic mild cognitive impairment (aMCI) and 25 Alzheimer’s disease dementia (AD) elderly individuals were included. All participants received comprehensive clinical and neuropsychological assessment based on the CERAD protocol, 11C-labeled Pittsburgh
Compound B (PiB) positron emission tomography, volumetric MRI, and quantification for serum thyroid hormone including total T3, free T4 and TSH. Global cerebral Ab deposition was defined as mean cortical PiB retention of the cortical regions including frontal, lateral temporal, lateral parietal and precuneus/posterior cingulate cortices. Results: Univariate analyses showed significant positive association of global cerebral Ab deposition with the levels of serum total T3 in total participants. In subgroup analysis, such association was found only in cognitively normal (CN) subjects, but not in MCI and AD patients. Independent positive associations between the levels of serum total T3 and global cerebral Ab deposition in CN participants were still significant even after controlling the effect of age, gender, apolipoprotein E ε4 genotype. Moreover, high serum T3 levels were significantly associated with poor global cognitive function measured by the total score of the CERAD neuropsychological test battery in CN participants. No association was found between both free T4 and TSH, and cortical 11C-PiB retention. Conclusions: Our findings indicate the association between thyroid hormone in blood, especially total T3 level, and the degree of cerebral amyloidosis in cognitively healthy elderly people. The mechanism underlying the relationship between the two needs to be further investigated.
P3-081 Table 1 Comparisons of serum thyroid hormone CN (n¼62)
aMCI (n¼29)
AD (n¼25)
Test value
p value
T3(mg/dL) 121.7 6 16.7 117.8 615.5 125.8 617.5 F(2.113)¼ 1.580 0.211 FreeT4(mg/dL) 1.08 60.22 1.15 6 0.19 1.14 6 0.21 F(2.113)¼ 1.517 0.224 TSH (mg/dL) 1.82 60.92 2.53 62.19 1.82 61.15 F(2.113)¼ 2.917 0.058
Date are presented as means 6 SD and anatyzed with ANOVA with degrees of freedom presented with the F values in the table. SD: standard deviation.CN: cognitively normal,aMCI: mild cognitive impairment. AD: Alzheimer’sdementia
Table 2 Pearson correlation of serum thyroid hormones with cerebral amyloid burden
overall participants (n¼116)
CN (n¼62)
aMCI (n¼29)
AD (n¼25)
Serum T3(mg/dL) Serum FreeT4(mg/dL) Serum TSH(mg/dL) Serum T3(mg/dL) Serum FreeT4(mg/dL) Serum TSH(mg/dL) Serum T3(mg/dL) Serum FreeT4(mg/dL) Serum TSH(mg/dL) Serum T3(mg/dL) Serum FreeT4(mg/dL) Serum TSH(mg/dL) Serum T3(mg/dL)
r
p
0.234 0.073 -0.017 0.332 -0.091 -0.010 0.002 0.051 0.035 0.319 0.104 -0.233 0.319
0.011* 0.438 0.855 0.008* 0.481 0.936 0.993 0.793 0.856 0.120 0.620 0.261 0.120
CN ¼ cognitively normal elderly, aMCI ¼ amnestic mild cognitive impairment, AD ¼ Alzheimer’s disease dementia
Poster Presentations: P3 Table 3 Partial correlation of serum thyroid hormone with cerebral amyloid burden in CN
Serum T3(mg/dL) Serum FreeT4(mg/dL) Serum TSH(mg/dL)
r
P
0.365 -0.031 -0.040
0.004* 0.817 0.762
CN ¼ cognitively normal elderly, partial correlation of serum thyroid hormone with cerebral amyloid burden controlling age, gender and ApoE e4 genotype, df ¼ 57
Table 4 Results from multiple regression analyses in CN (n ¼ 62) Independent Dependent variable variable
B
SE
t
P
R2
F F(4,57) ¼ 2.913
Cerebral amyloid burden Age Gender ApoE ε4 genotype Serum T3 level
.005 -.005 .105 .004
.004 .043 .061 .001
1.241 -.108 1.720 2.962
.111
.220 .914 .091 .004 F(4,57) ¼ 0.638 -0.024
Cerebral amyloid burden Age Gender ApoE ε4 genotype Serum T4 level
.002 -.008 .098 -.027
.004 .498 .621 .050 -.154 .878 .069 1.398 .168 .118 -.232 .817 F(4,57) ¼ 0.648 -0.024
Cerebral amyloid burden Age Gender ApoE ε4 genotype Serum TSH level
.003 -.013 .101 -.008
.004 .596 .554 .046 -.274 .785 .066 1.540 .129 .027 -.304 .762
CN ¼cognitively normal elderly, B ¼ Regression coefficient, SE ¼ Standard error.
Table 5 Partial correlation of serum T3 with cognition in CN elderly
CERAD total scorel (TS1) CERAD total score2(TS2)
r
P
-0.312 -0.295
0.018* 0.026*
Partial correlation of serum T3 with cognition controlling age, gender and education, df ¼ 55
ASSOCIATIONS BETWEEN BDNF SERUM LEVELS AND ALZHEIMER’S DISEASE-RELATED MEASURES: THE FRAMINGHAM STUDY Galit Weinstein1, Sarah R. Preis2,3, Alexa S. Beiser2,3, Claudia L. Satizabal4,5, Nicole L. Spartano4, Tai C. Chen4, Vasan S. Ramachandran4,5, Sudha Seshadri4,5, 1University of Haifa, Haifa, Israel; 2Boston University School of Public Health, Boston, MA, USA; 3The Framingham Study, Framingham, MA, USA; 4Boston University School of Medicine, Boston, MA, USA; 5The Framingham Heart Study, Framingham, MA, USA. Contact e-mail: [email protected] Background: Brain derived neurotrophic factor (BDNF) may play a role in the pathogenesis of Alzheimer’s disease (AD) through neurotrophic effects on basal cholinergic neurons. We have previously
P649
shown that among cognitively intact individuals, reduced serum levels predict AD risk. Thus, we have now examined the association of various demographic, behavioral and clinical AD related measures with serum BDNF levels. Methods: BDNF was measured in 3,689 participants (mean age 65 years, 56% women) from the Framingham Study’s Original (n¼669) and Offspring (n¼3,020) cohorts. Linear regression was used to evaluate the cross-sectional relationship between AD related measures (waist-hip ratio, waist circumference, body mass index, systolic blood pressure, hypertension, hypertension treatment, current cigarette smoking, alcohol use, diabetes, total cholesterol, HDL cholesterol, statin use, history of CVD, history of atrial fibrillation, and APOE4) and BDNF. Presence of depressive symptoms, score on a physical activity index, total caloric intake, renal function (estimated glomerular function rate), and circulating levels of triglycerides, C-reactive protein, TNF-alpha and homocysteine were also assessed but only in the Offspring cohort. Results: Participants with serum BDNF levels at the bottom two quintiles compared to the rest were older (p¼0.03) and more likely to be males (p<0.001). Adjusting for age and sex, higher BDNF levels were observed among current smokers compared to former or never smokers (b[SE]¼2286 [427], p-value<0.0001), and to a lesser extent among persons who are physically active (b[SE]¼ 51.0[24.3], p-value¼0.04 for a unit elevation in physical activity index) and who have high total-cholesterol (b[SE]¼19.4[3.7], p-value<0.0001). In addition, BDNF levels were lower among persons with prevalent atrial fibrillation (b[SE]¼-1942.3[670.8], p-value¼0.004), and were negatively associated with circulating TNF-a levels (b[SE]¼-974 [358], p-value¼0.007). Conclusions: BDNF may be modulated by behavioral and clinical factors which, in turn, are associated with AD risk. Thus physical activity, atrial fibrillation and inflammation may increase AD risk partly through changes in BDNF levels. Conversely, higher BDNF levels in current smokers could partially explain prior conflicting reports on the association of current smoking with AD risk, serving to mitigate the expected adverse effects. Mediation analyses to further explore the possible role of BDNF in the AD causal pathway will be presented.
P3-082
COMPROMISED REGULATION OF SERUM CYTOKINE LEVELS AND BDNF DUE TO LOW LEVELS OF VITAMIN D IN PATIENTS WITH EARLY- OR LATE-ONSET ALZHEIMER’S DISEASE OR PARKINSON’S DISEASE
Duygu Gezen-Ak1, Bas¸ar Bilgic¸2, Has¸met Hanagası2, Sibel Ertan1, € ur S. Araz1, Ebba Lohmann2, Irem L. Atasoy1, Merve Alaylıoglu1, Om€ € 1, Ays¸eg€ul G€und€uz1, G€unes¸ Kızıltan2, H€ulya Apaydın1, Burak Onal Hakan I. Gurvit2, Selma Yılmazer1, Erdinc Dursun1, 1Istanbul University, Cerrahpasa Faculty of Medicine, Istanbul, Turkey; 2Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey. Contact e-mail: [email protected] Background: Neurodegenerative disorders like Alzheimer’s disease (AD), Parkinson’s disease (PD) were suggested to involve neuroinflammation as part of the pathogenesis. Interleukin-1-beta (IL-1b), interleukin-6 (IL-6), tumor-necrosis-factor-alpha (TNFa) are inflammatory cytokines contribute to neuroinflammation in these disorders. Brain derived neurotrophic factor (BDNF) participates in learning, memory, and behavior. Vitamin D is a seco-steroid hormone that has the capacity regulate immune response and neurotrophic factor synthesis. Methods: The circulating form of vitamin D in blood (25OHD) is measured in four patient groups including AD