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Authors: Shinto, Lynne | Quinn, Joseph | Montine, Thomas | Dodge, Hiroko H. | Woodward, William | Baldauf-Wagner, Sara | Waichunas, Dana | Bumgarner, Lauren | Bourdette, Dennis | Silbert, Lisa | Kaye, Jeffrey

Article Type: Research Article

Abstract: Oxidative stress, inflammation, and increased cholesterol levels are all mechanisms that have been associated with Alzheimer's disease (AD) pathology. Several epidemiologic studies have reported a decreased risk of AD with fish consumption. This pilot study was designed to evaluate the effects of supplementation with omega-3 fatty acids alone (ω-3) or omega-3 plus alpha lipoic acid (ω-3 + LA) compared to placebo on oxidative stress biomarkers in AD. The primary outcome measure was peripheral F2-isoprostane levels (oxidative stress measure). Secondary outcome measures included performance on: Mini-Mental State Examination (MMSE), Activities of Daily Living/Instrumental Activities of Daily Living (ADL/IADL), and Alzheimer Disease …Assessment Scale-cognitive subscale (ADAS-cog). Thirty-nine AD subjects were randomized to one of three groups: 1) placebo, 2) ω-3, or 3) ω-3 + LA for a treatment duration of 12 months. Eighty seven percent (34/39) of the subjects completed the 12-month intervention. There was no difference between groups at 12 months in peripheral F2-isoprostane levels (p = 0.83). The ω-3 + LA and ω-3 were not significantly different than the placebo group in ADAS-cog (p = 0.98, p = 0.86) and in ADL (p = 0.15, p = 0.82). Compared to placebo, the ω-3 + LA showed less decline in MMSE (p < 0.01) and IADL (p = 0.01) and the ω-3 group showed less decline in IADL (p < 0.01). The combination of ω-3 + LA slowed cognitive and functional decline in AD over 12 months. Because the results were generated from a small sample size, further evaluation of the combination of omega-3 fatty acids plus alpha-lipoic acid as a potential treatment in AD is warranted. Show more

Keywords: Alpha-lipoic acid, Alzheimer's disease, clinical trial, omega-3 fatty acids

DOI: 10.3233/JAD-130722

Citation: Journal of Alzheimer's Disease, vol. 38, no. 1, pp. 111-120, 2014

Authors: Abdi, Fadi | Quinn, Joseph F. | Jankovic, Joseph | McIntosh, Martin | Leverenz, James B. | Peskind, Elaine | Nixon, Randy | Nutt, John | Chung, Katherine | Zabetian, Cyrus | Samii, Ali | Lin, Melanie | Hattan, Stephen | Pan, Catherine | Wang, Yan | Jin, Jinghua | Zhu, David | Li, G. Jane | Liu, Yan | Waichunas, Dana | Montine, Thomas J. | Zhang, Jing

Article Type: Research Article

Abstract: Biomarkers are needed to assist in the diagnosis and medical management of various neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and dementia with Lewy body (DLB). We have employed a multiplex quantitative proteomics method, iTRAQ (isobaric Tagging for Relative and Absolute protein Quantification), in conjunction with multidimensional chromatography, followed by tandem mass spectrometry (MS/MS), to simultaneously measure relative changes in the proteome of cerebrospinal fluid (CSF) obtained from patients with AD, PD, and DLB compared to healthy controls. The diagnosis of AD and DLB was confirmed by autopsy, whereas the diagnosis of PD was based on clinical criteria. …The proteomic findings showed quantitative changes in AD, PD, and DLB as compared to controls; among more than 1,500 identified CSF proteins, 136, 72, and 101 of the proteins displayed quantitative changes unique to AD, PD, and DLB, respectively. Eight unique proteins were confirmed by Western blot analysis, and the sensitivity at 95% specificity was calculated for each marker alone and in combination. Several panels of unique makers were capable of distinguishing AD, PD and DLB patients from each other as well as from controls with high sensitivity at 95% specificity. Although these preliminary findings must be validated in a larger and different population of patients, they suggest that a roster of proteins may be generated and developed into specific biomarkers that could eventually assist in clinical diagnosis and monitoring disease progression of AD, PD and DLB. Show more

Keywords: Alzheimer disease, biomarkers, Parkinson disease, proteomics

DOI: 10.3233/JAD-2006-9309

Citation: Journal of Alzheimer's Disease, vol. 9, no. 3, pp. 293-348, 2006