Friday, 7 March 2014

Alzheimer's disease in Foods Points of View

Kyle J. Norton

Alzheimer's disease is a brain disorder correlated with major reductions of neurons to the respective target areas, named after German physician Alois Alzheimer. Alzheimer's destroys brain cells, causing cognitive modalities severe enough to affect language communication, memory, lifelong hobbies or social life. Alzheimer's gets worse over time, and it is fatal. 
According to statistic, over 25 million people in the world today are affected by dementia and most are suffering from Alzheimer's disease. It may be a result of  cigarette smoking, midlife high blood pressure and obesity, diabetes, and cerebrovascular lesions and psychosocial factors (eg, high education, active social engagement, physical exercise, and mentally stimulating activity)(1) Strong evidences emerged in epidemiological studies suggested that certain foods(2) may have potential in reduced risk and treatments of Alzheimer's disease.

1. Cruciferous vegetables
Cruciferous vegetables are the group of vegetables belonging to the family Brassicaceae, including cauliflower, cabbage, cress, bok choy, broccoli etc..
Epidemiological studies has demonstrated reduced risk of Alzheimer's disease in cruciferous consumption. The study of 2148 community-based elderly subjects (aged > or = 65 years) without dementia in New York, after 3.9 years,  253 subjects developed AD during a follow-up. Dietary pattern (DP) analysis of food combination indicated that higher intakes of salad dressing, nuts, fish, tomatoes, poultry, cruciferous vegetables, fruits, and dark and green leafy vegetables and a lower intake of high-fat dairy products, red meat, organ meat, and butter are associated to reduced risk of  AD.(1)

2. Tomatos
Tomato is a red, edible fruit, genus Solanum, belonging to family Solanaceae, native to South America. Because of its health benefits, tomato is grown world wide for commercial purpose and often in green house.
Lycopene and alpha carotene found in tometos inhibited symptoms of AD through inhibition of amyloid beta (Aβ) formation, deposition and fibril formation either by reducing the levels of p35 or inhibiting corresponding enzymes(2). In the study of Antioxidants, such as tocopherols and carotenoids,  implicated in the prevention of degenerative diseases showed that aging population exhibit a age related decline of levels retinol, total tocopherols, total xanthophylls and total carotenoids(3).

3. Garlic
Garlic is a natural superfood healer for its natural antibiotic with antiviral, antifungal, anticoagulant and antiseptic properties.
 S-allyl-L-cysteine (SAC), an active chemical constituents of garlic, showed to inhibit several pathological cascades related to the synaptic degeneration and neuroinflammatory pathways associated with AD. through up and down regulations(4) with intervention to prevent free radicals causes of deterioration of cognitive functions and neurobehavioral activities(5). The Central Food Technological Research Institute supported the binding ability of SAC to Abeta, inducing a partially folded conformation in Abeta.(6) and suggested that consumption of garlic may reduced risk of AD, due to inhibition of Abeta aggregation in human brain(7).

4. Ginger
Ginger (
Zingiber officinale) or ginger root is the genus Zingiber, belonging to the family Zingiberaceae, native to Tamil. It has been used in traditional and Chinese medicine to treat dyspepsia, gastroparesis, constipation, edema, difficult urination, colic, etc.

In the Alzheimer disease (AD) rat model, ginger root extract (GRE) administered intra-gastrically to rats after 35 days, exhibited the protective effect against AD through reversed behavioral dysfunction and prevented AD-like symptoms(8).  [6]-gingerol, a pungent ingredient of ginger, pretreatment protected against Aβ(25-35)-induced cytotoxicity and apoptotic cell death such as DNA fragmentation, disruption of mitochondrial membrane potential, elevated Bax/Bcl-2 ratio, and activation of caspase-3 via augmentation of antioxidant capacity(9) and inhibition of acetylcholinesterase activities and prevention of lipid peroxidation in the brain(10).

5. Turmeric
Turmeric is a perennial plant in the genus Curcuma, belonging to the family Zingiberaceae, native to tropical South Asia. The herb has been used in traditional medicine as anti-oxidant, hypoglycemic, colorant, antiseptic, wound healing agent, and to treat flatulence, bloating, and appetite loss, ulcers, eczema, inflammations, etc.

Evidences of epidemiological studies suggestion of curcumin in reduced risk of Ad progression. Suggestion of curcumin in treating Alzheimer's disease (AD) depended on the ability to penetrate the blood-brain barrier(11) and on inhibited progression of deposit of  beta-amyloid aggregation.(12).
A novel polymeric nanoparticle (PEG-PLGA) encapsulated curcumin, induced adult neurogenesis through activation of the canonical Wnt/β-catenin pathway(secreted signalling proteins  released by one cell population will trigger concentration-dependent responses in other cells located some distance away)(13) and brain self-repair mechanis(14).  Unfortunately, a 24-week randomized, double blind, placebo-controlled study conducted by the David Geffen School of Medicine at UCLA, oral administration showed no biochemical evidence of efficacy of Curcumin C3 Complex® in AD(15).

6. Cinnamon
Cinnamon is a spice derived from the inner bark of tree, native to South East Asia, of over 300 species of the genus Cinnamomum, belonging to the family Lauraceae.. The herb has been use in herbal and traditional medicine as anti-fungal and bacteria level to improve reproductive organ, prevent flatulence and intestinal cramping, treat indigestion, diarrhea, bad breath, headache, migraine, etc.
Aqueous extract of cinnamon showed to inhibit tau aggregation in vitro and can even induce dissociation of tangles isolated from AD brain and cinnamaldehyde (CA). The organic compound of cinnamon
protected tau from oxidation caused by the reactive oxygen species, H2O2, and prevented subsequent formation of high molecular weight species that are considered to stimulate tangle formation(16) and inhibited tau aggregation associated with Alzheimer's disease in vitro(17). Other study insisted that cinnamon extract (CEppt), markedly inhibits the formation of toxic Aβ oligomers and prevents the toxicity of Aβ on neuronal PC12 cells and oral administration in AD patients, showed to reduce longevity, fully recovered their locomotion defects and totally abolished tetrameric species of Aβ in the brain(18).

7. Black pepper
Black pepper is a  is a flowering vine in the genus Pipper, belonging to the family Piperaceae. It has been used in folk medicine in treating constipation, diarrhea, earache, gangrene, heart disease, hernia, hoarseness, indigestion, insect bites, insomnia, joint pain, etc.
Piperine, a main active alkaloid in black pepper exhibited significantly improved memory impairment and neurodegeneration in hippocampus associated with the decrease lipid peroxidation and acetylcholinesterase enzyme(19). In the evaluation the Piperine therapeutic effects in Alzheimer's Disease, at 2 mg/kg dose, reduced the SOD values, immobility and has shown superior results than Donepezil (5 mg/kg), AD drug and increased the acetylcholenesterase values(20).

8. Green Tea
Green tea contains more amount of antioxidants than any drinks or food with the same volume, and is the leaves of Camellia sinensis, undergone minimal oxidation during processing, originated from China. Green tea has been a precious drink in traditional Chinese culture and used exceptional in socialization for more than 4000 thousand years. Because of their health benefits, they have been cultivated for commercial purposes all over the world.
Green tea polyphenols (GTPs) may be a next potential agent in protection of neurodegenerative diseases such as Alzheimer's disease (AD). GTPs have found to inhibit amyloid fibril formation and protect neurons from toxicity induced by β-amyloid and OA-induced neurotoxicity by enhancing the amelioration of learning and memory impairments and also reduction of tau hyperphosphorylation(21). Epigallocatechin gallate polyphenols, isolated from green tea, a selective inhibitor of PKC., combination of EGCG and resveratrol protected against GF 109203X-induced cell death and cytoskeleton degeneration, with a maximal effect at 1 and 3 μM, respectively and cells treated increased PKC gamma (γ) activation and promoted neuronal interconnections(22). (-)-epigallocatechin-3 gallate (EGCG) alone also showed to reduce amyloid-β (Aβ) production in both neuronal and mouse Alzheimer's disease (AD) models(23).

9. Coffee
Coffee made from the roasted seeds of the genus Coffee, belonging to the family Rubiaceae native to southern Arabia. Coffee may consist certain substances, effecting the risk of Alzheimers' disease. AD mice given caffeine in their drinking water from young adulthood into older age showed to inhibit memory and cognitive impairment and lower brain levels of amyloid-beta; Abeta)(24)(25). In mice with Alzheimers' disease caused by dysregulated endoplasmic reticulum (ER) calcium (Ca 2+), induced deletion of RyanR3, showed the enhancement of coffee in activation of RyanRs which protected AD neurons from synaptic and network dysfunction(26). Intake of 5 cups of coffee per day(moderate caffeine intake) found to protect against the development of certain cognitive impairment and decreased hippocampal amyloid-beta (Abeta) levels through suppression of both beta-secretase (BACE1), a beta-site amyloid precursor protein cleaving enzyme 1 and presenilin 1 (PS1)/gamma-secretase expression(mutations in the presenilin proteins)(27)(28).

10. Red wine
Red wine made from made  dark-coloured (black) grape varieties as a result of anthocyan pigments  present in the skin of the grape.
Red wine may be a therapeutic potential  for treating AD patients through reduction of forming of beta-amyloid peptid. In human umbilical vein endothelial cells (HUVECs), black grape skin extract inhibited the ROS production, protected the cellular membrane from oxidative damage, and consequently prevented DNA fragmentation(29).  Red wine extract resveratrol, in another study inhibited the expression of soluble oligomers of the amyloid-β (Aβ) peptide cause of neurotoxicity, synaptic dysfunction, and memory impairments(30). Polyphenols derived from red wine, according to Mount Sinai School of Medicine, New York, may protect against cognitive deterioration of Alzheimer's disease, thriugh generation and assembly of β-amyloid peptides into neurotoxic oligomeric aggregated species(31).

10. Olive oil
Olive is belongs to the the family Oleaceae, native to the coastal areas of the eastern Mediterranean Basin and south end of the Caspian Sea. Its fruit, is also called the olive and the source of olive oil.
Oleuropein aglycone, the main polyphenol derived from extra virgin olive oil, in the study of the double transgenic TgCRND8 mice, showed to improve the cognitive performance and reduce ß-amyloid levels and plaque deposits, through  increase of autophagic markers expression and of lysosomal (break down waste materials and cellular debris)activity(32), induction of the Aβ transgene expression(33) and enhancement of Aβ clearance from the brain(34). The study by VA Medical Center, also found that EVOO inhibited learning and memory deficits found in aging and diseases, due to overproduction of amyloid-β protein, and reversed oxidative damage in the brain(35).

11. Fish oil
Fish oil derived from the tissues of oily fish, contains high amount of omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), etc.
Epidemiological studies suggested that higher dietary intake of ω-3 PUFA reduced risk of incident AD and slower cognitive decline(36) through reduction of plasma levels of Aβ42(37) and may be through induced the PTEN expression(ova tumor suppressor gene) by activation of peroxisome proliferator-activated receptor(regulating the expression of genes)(38). Genetically, defection of the ε4 allele of the APOE gene (APOE4), according to the Central Michigan University, in the mu-p75 saporin (SAP)-induced mouse model of AD, daily treatments of Cerise(®) Total-Body-Rhythm™ (TBR; containing tart cherry extract, Nordic fish oil, and refined emu oil), reduced the severity of cognitive deficits in disorders involving cholinergic deficits(39). 

Taking altogether, without going into reviews, The list of foods above may be effective in reduced risk and treatment of Alzheimers' disease through improvement of cognitive function, via reduced plasma levels of Aβ42 and ß-amyloid and plaque deposits. Some researchers suggested that larger sample and multi centers studies are necessary to identify the principle ingredients for validation of their effectiveness. As always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying.

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(1) Food combination and Alzheimer disease risk: a protective diet by Gu Y1, Nieves JW, Stern Y, Luchsinger JA, Scarmeas N.(PubMed)
(2) Carotenoids and Alzheimer's disease: an insight into therapeutic role of retinoids in animal models by Obulesu M1, Dowlathabad MR, Bramhachari PV.(PubMed)
(3) Carotenoid, tocopherol, and retinol concentrations in elderly human brain by Craft NE1, Haitema TB, Garnett KM, Fitch KA, Dorey CK.(PubMed)
(4) The "aged garlic extract:" (AGE) and one of its active ingredients S-allyl-L-cysteine (SAC) as potential preventive and therapeutic agents for Alzheimer's disease (AD) by Ray B1, Chauhan NB, Lahiri DK.(PubMed)
(5) S-allyl cysteine attenuates oxidative stress associated cognitive impairment and neurodegeneration in mouse model of streptozotocin-induced experimental dementia of Alzheimer's type by Javed H1, Khan MM, Khan A, Vaibhav K, Ahmad A, Khuwaja G, Ahmed ME, Raza SS, Ashafaq M, Tabassum R, Siddiqui MS, El-Agnaf OM, Safhi MM, Islam F.(PubMed)
(6) Anti-amyloidogenic activity of S-allyl-L-cysteine and its activity to destabilize Alzheimer's beta-amyloid fibrils in vitro by Gupta VB1, Rao KS.(PubMed)
(7) Garlic extract exhibits antiamyloidogenic activity on amyloid-beta fibrillogenesis: relevance to Alzheimer's disease by Gupta VB1, Indi SS, Rao KS(PubMed)
(8) Protective effects of ginger root extract on Alzheimer disease-induced behavioral dysfunction in rats by Zeng GF1, Zhang ZY, Lu L, Xiao DQ, Zong SH, He JM.(PubMed)
(9) [6]-Gingerol attenuates β-amyloid-induced oxidative cell death via fortifying cellular antioxidant defense system by Lee C1, Park GH, Kim CY, Jang JH.(PubMed)
(10) Inhibition of acetylcholinesterase activities and some pro-oxidant induced lipid peroxidation in rat brain by two varieties of ginger (Zingiber officinale) by Oboh G1, Ademiluyi AO, Akinyemi AJ.(PubMed)

(11) Highly stabilized curcumin nanoparticles tested in an in vitro blood-brain barrier model and in Alzheimer's disease Tg2576 mice by Cheng KK1, Yeung CF, Ho SW, Chow SF, Chow AH, Baum L.(PubMed)
(12) Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study by Ringman JM1, Frautschy SA, Teng E, Begum AN, Bardens J, Beigi M, Gylys KH, Badmaev V, Heath DD, Apostolova LG, Porter V, Vanek Z, Marshall GA, Hellemann G, Sugar C, Masterman DL, Montine TJ, Cummings JL, Cole GM.(PubMed)
(13) Curcumin-Loaded Nanoparticles Potently Induce Adult Neurogenesis and Reverse Cognitive Deficits in Alzheimer's Disease Model via Canonical Wnt/β-Catenin Pathway by Tiwari SK1, Agarwal S, Seth B, Yadav A, Nair S, Bhatnagar P, Karmakar M, Kumari M, Chauhan LK, Patel DK, Srivastava V, Singh D, Gupta SK, Tripathi A, Chaturvedi RK, Gupta KC.(PubMed)
(14) Curcumin-Loaded Nanoparticles Potently Induce Adult Neurogenesis and Reverse Cognitive Deficits in Alzheimer's Disease Model via Canonical Wnt/β-Catenin Pathway by Tiwari SK1, Agarwal S, Seth B, Yadav A, Nair S, Bhatnagar P, Karmakar M, Kumari M, Chauhan LK, Patel DK, Srivastava V, Singh D, Gupta SK, Tripathi A, Chaturvedi RK, Gupta KC.(PubMed)
(15) Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study by Ringman JM1, Frautschy SA, Teng E, Begum AN, Bardens J, Beigi M, Gylys KH, Badmaev V, Heath DD, Apostolova LG, Porter V, Vanek Z, Marshall GA, Hellemann G, Sugar C, Masterman DL, Montine TJ, Cummings JL, Cole GM.(PubMed)
(16) Interaction of cinnamaldehyde and epicatechin with tau: implications of beneficial effects in modulating Alzheimer's disease pathogenesis by George RC1, Lew J, Graves DJ.(PubMed)
(17) Cinnamon extract inhibits tau aggregation associated with Alzheimer's disease in vitro by Peterson DW1, George RC, Scaramozzino F, LaPointe NE, Anderson RA, Graves DJ, Lew J.(PubMed)
(18) Orally administrated cinnamon extract reduces β-amyloid oligomerization and corrects cognitive impairment in Alzheimer's disease animal models by Frydman-Marom A1, Levin A, Farfara D, Benromano T, Scherzer-Attali R, Peled S, Vassar R, Segal D, Gazit E, Frenkel D, Ovadia M(PubMed)
(19) Piperine, the main alkaloid of Thai black pepper, protects against neurodegeneration and cognitive impairment in animal model of cognitive deficit like condition of Alzheimer's disease. by Chonpathompikunlert P1, Wattanathorn J, Muchimapura S.(PubMed)
(20) Preparation, characterization, in vivo and biochemical evaluation of brain targeted Piperine solid lipid nanoparticles in an experimentally induced Alzheimer's disease model by Yusuf M1, Khan M, Khan RA, Ahmed B.(PubMed)
(21) Green tea polyphenols protect against okadaic acid-induced acute learning and memory impairments in rats by Li H1, Wu X1, Wu Q1, Gong D1, Shi M1, Guan L1, Zhang J1, Liu J1, Yuan B1, Han G2, Zou Y3(PubMed)
(22) Neuroprotective effects of resveratrol and epigallocatechin gallate polyphenols are mediated by the activation of protein kinase C gamma. Menard C1, Bastianetto S2, Quirion R3(PubMed)
(23) Octyl gallate markedly promotes anti-amyloidogenic processing of APP through estrogen receptor-mediated ADAM10 activation by Zhang SQ1, Sawmiller D, Li S, Rezai-Zadeh K, Hou H, Zhou S, Shytle D, Giunta B, Fernandez F, Mori T, Tan J.(PubMed)
(24) Caffeine and coffee as therapeutics against Alzheimer's disease by Arendash GW1, Cao C.(PubMed)
(25) Caffeine reverses cognitive impairment and decreases brain amyloid-beta levels in aged Alzheimer's disease mice by Arendash GW1, Mori T, Cao C, Mamcarz M, Runfeldt M, Dickson A, Rezai-Zadeh K, Tane J, Citron BA, Lin X, Echeverria V, Potter H.(PubMed)
(26) The role of ryanodine receptor type 3 in a mouse model of Alzheimer disease by Liu J1, Supnet C2, Sun S1, Zhang H1, Good L3, Popugaeva E4, Bezprozvanny I5.(PubMed)
(27) Caffeine reverses cognitive impairment and decreases brain amyloid-beta levels in aged Alzheimer's disease mice by Arendash GW1, Mori T, Cao C, Mamcarz M, Runfeldt M, Dickson A, Rezai-Zadeh K, Tane J, Citron BA, Lin X, Echeverria V, Potter H.(PubMed)
(28) Caffeine and coffee as therapeutics against Alzheimer's disease by Arendash GW1, Cao C.
(29) Red wine micronutrients as protective agents in Alzheimer-like induced insult by Russo A1, Palumbo M, Aliano C, Lempereur L, Scoto G, Renis M.(PubMed)
(30) rion protein-mediated toxicity of amyloid-β oligomers requires lipid rafts and the transmembrane LRP1 by Rushworth JV1, Griffiths HH, Watt NT, Hooper NM(PubMed)
(31) Novel role of red wine-derived polyphenols in the prevention of Alzheimer's disease dementia and brain pathology: experimental approaches and clinical implications by Pasinetti GM.(PubMed)
(32) The polyphenol oleuropein aglycone protects TgCRND8 mice against Aß plaque pathology by Grossi C1, Rigacci S, Ambrosini S, Dami TE, Luccarini I, Traini C, Failli P, Berti A, Casamenti F, Stefani M(PubMed)
(33) Oleuropein aglycone protects transgenic C. elegans strains expressing Aβ42 by reducing plaque load and motor deficit by Diomede L1, Rigacci S, Romeo M, Stefani M, Salmona M(PubMed)
(34) Olive-oil-derived oleocanthal enhances β-amyloid clearance as a potential neuroprotective mechanism against Alzheimer's disease: in vitro and in vivo studies by Abuznait AH1, Qosa H, Busnena BA, El Sayed KA, Kaddoumi A(PubMed).
(35) Extra virgin olive oil improves learning and memory in SAMP8 mice by Farr SA1, Price TO, Dominguez LJ, Motisi A, Saiano F, Niehoff ML, Morley JE, Banks WA, Ercal N, Barbagallo M.(PubMed)
(36) Current evidence for the clinical use of long-chain polyunsaturated n-3 fatty acids to prevent age-related cognitive decline and Alzheimer's disease by Dacks PA1, Shineman DW, Fillit HM.(PubMed)
(37) Nutrient intake and plasma β-amyloid by Gu Y1, Schupf N, Cosentino SA, Luchsinger JA, Scarmeas N.(PubMed)
(38) Diets involved in PPAR and PI3K/AKT/PTEN pathway may contribute to neuroprotection in a traumatic brain injury by Kitagishi Y1, Matsuda S.(PubMed)
(39) Combinatorial treatment of tart cherry extract and essential fatty acids reduces cognitive impairments and inflammation in the mu-p75 saporin-induced mouse model of Alzheimer's disease.

Matchynski JJ1, Lowrance SA, Pappas C, Rossignol J, Puckett N, Sandstrom M, Dunbar GL.(PubMed)

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