User:JohnLloydScharf/Alzheimer.27s Disease

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Alzheimer's Disease[edit]


10 Warning Signs of Alzheimer’s[edit]

http://www.alz.org/national/documents/checklist_10signs.pdf

My Mother's side of the family has late age Alzheimer's after 70[edit]

Documented Risk Alleles[edit]




  • "rs737865","22","18310121","AA" Risk Allele is A
http://www.nature.com/mp/journal/v10/n11/fig_tab/4001709t2.html#figure-title
http://omim.org/entry/104300#reference169
http://omim.org/entry/104300
http://www.snpedia.com/index.php/Rs737865


  • "rs7412","19","50103919","CC"
Risk or phenotype-associated allele: The APOE E4 allele is a combination of rs429358 C (130Arg) and rs7412 C (176Arg)
http://www.snpedia.com/index.php/Rs7412


I am an rs7019241(C;T) (chr9 86,078,545 plus) reduced risk for AD?:rs7019241(C;C) average
rs7019241(C;T) reduced risk for AD?
rs7019241(T;T) reduced risk for AD?
http://www.snpedia.com/index.php/Rs7019241


Orientation minusI am an rs669(A;G) 23andme equivalent rs669(C;T) (chr12 9,079,672 minus) possibly increased risk for Alzheimers
Rs669(A;A) 0 normal
Rs669(A;G) possibly increased risk for Alzheimers
Rs669(G;G) 2 3.8x or higher increased risk for Alzheimers
http://www.snpedia.com/index.php/Rs669


Orientation minus
I am an rs2254958(G;G) (chr2 37,149,148 plus)
Rs2254958(A;A) 0
Rs2254958(C;C) 1.61x increased risk for Alzheimer's
Rs2254958(C;T) 1.24x increased risk for Alzheimer's
Rs2254958(T;T) 0 common
http://www.snpedia.com/index.php/Rs2254958


I am an rs9886784(A;C) (chr9 1,521,204 plus) 3.23x risk for Alzheimer's disease
rs9886784(A;A) >3.2x risk for AD
rs9886784(A;C) 3.2x risk for AD
rs9886784(C;C) average
http://www.snpedia.com/index.php/Rs9886784(A;C)
  • rs9886784, a intergenic SNP on chromosome 9, is reported to influence the risk for Alzheimer's disease based on a study of ~1100 Canadian patients. THe risk allele is (A); the odds ratio is 3.23


I am an rs5984894(G;G) (chrX 92,138,738 plus) normal

rs5984894(A;A) 1.75x increased risk for Alzheimer's disease in females (as compared to (G;G) females)
rs5984894(A;G) 1.26x increased risk for Alzheimer's disease in females (as compared to (G;G) females)
rs5984894(G;G) normal
http://www.snpedia.com/index.php/Rs5984894
Normal
http://www.snpedia.com/index.php/Rs5984894(G;G)


Misc. Research Papers[edit]

  • No therapeutic effect of dietary omega-3 fatty acid and curcumin in dementia and Alzheimer's disease
http://www.jneurosci.org/content/29/28/9078.full/reply#jneuro_el_21841

"...Specifically, individuals with a higher fish intake had a risk of developing dementia or AD similar to that of those who usually did not eat fish...Based on these findings, the use of omega-3 FA and/or curcumin to preserve cognitive function in the elderly seems not to have any scientific basis...." ?Beta-Amyloid Oligomers Induce Phosphorylation of Tau and Inactivation of Insulin Receptor Substrate via c-Jun N-Terminal Kinase Signaling: Suppression by Omega-3 Fatty Acids and Curcumin http://www.jneurosci.org/content/29/28/9078.full.pdf

  • Morphological Characterization of Thioflavin-S-Positive Amyloid Plaques in Transgenic Alzheimer Mice and Effect of Passive A? Immunotherapy on Their Clearance
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1618604/
  • AA Species Removal After AA42 Immunization
http://www.med.upenn.edu/timm/documents/Abetavaccinepathology.pdf
  • Amyloid-? immunotherapy for Alzheimer’s disease: the end of the beginning
http://homepage.mac.com/sanagnos/schenk2002.pdf
  • Calcineurin inhibition with FK506 ameliorates dendritic spine density deficits in plaque-bearing Alzheimer model mice.
http://www.ncbi.nlm.nih.gov/pubmed/19734903
  • Can Alzheimer disease be prevented by amyloid-? immunotherapy?
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2864089/
  • Anti-amyloid-? immunotherapy in Alzheimer's disease: relevance of transgenic mouse studies to clinical trials
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2615484/
  • Beneficial effect of human anti-amyloid-? active immunization on neurite morphology and tau pathology
http://brain.oxfordjournals.org/content/133/5/1312.full
  • Perspective: Prevention is better than cure
Attempts to reduce amyloid-? in the brain have yet to show clinical benefits. Starting treatment early is the best hope, says Sam Gandy
http://www.nature.com/nature/journal/v475/n7355_supp/full/475S15a.html
  • A?-Immunotherapy for Alzheimer's Disease Using Mannan–Amyloid-Beta Peptide Immunoconjugates
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2048489/
  • Alzheimer's disease: new mechanisms for an old problem
http://www.umdnj.edu/research/publications/fall06/4.htm
http://www.umdnj.edu/research/publications/fall06/Research_Fall06.pdf
  • Phase 2 Safety Trial Targeting Amyloid ? Production With a -Secretase Inhibitor in Alzheimer Disease
http://archneur.ama-assn.org/cgi/content/abstract/65/8/1031
  • Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial.
http://www.ncbi.nlm.nih.gov/pubmed/21045096
CONCLUSION-Supplementation with DHA compared with placebo did not slow the rate of cognitive and functional decline in patients with mild to moderate Alzheimer disease.

(A?)-induced complement system activation plays an important role in Alzheimer's disease (AD)[edit]

Complement receptor 1 (CR1) is thought to contribute to A? clearance. A recent large genome-wide association study (GWAS) has identified significant association of two single nucleotide polymorphisms (SNPs) (rs6656401 and rs3818361) in the CR1 gene with AD in Caucasians. Here, we performed a case–control study to clarify whether the risk for sporadic late-onset AD (LOAD) might be influenced by these polymorphisms in a large Chinese cohort consisting of 254 patients and 357 healthy controls. The results revealed that there were significant differences in genotype (P = 0.02) and allele (P = 0.007) frequencies of the SNP rs6656401 but none in rs3818361 between AD patients and controls. The A allele of rs6656401 was associated with an increased risk of LOAD (P = 0.007, odds ratios/OR = 1.652). In the subgroup of APOE ?4 non-carriers, both the A of rs6656401 and T allele of rs3818361 were observed to be significantly higher in case than in controls (P = 0.002 and P = 0.035, respectively). For rs6656401, the logistic regression analysis revealed that the (AA + AG) genotypes has a 2.4-fold increased risk compared with the GG genotype (P = 0.049). Haplotype analysis identified the AT haplotype to increase the risk of LOAD (P = 0.03, OR = 2.44). This study provides the evidence that variations in the CR1 gene play an important role in the pathogenesis of sporadic LOAD in the Han Chinese population.

CR1 205758672 rs6656401 A or G GG

MY SUSPECT SNPS FOR LOAD:[edit]

  • Rs157580-P=1.3E-07 for Minor Allele G
TOMM40 50087106 rs157580 A or G AG
  • APP amyloid beta (A4) precursor protein
APP 26247299 rs11306462 -/T DD
APP 26421399 rs35029493 -/A II
APP 26194030 rs380417 C or T CT
APP 26206976 rs2829983 G or T GT
APP 26209795 rs214488 A or G AG=CT
APP 26226123 rs2829984 C or T CT
APP 26258039 rs216762 C or T CT
APP 26266108 rs2051174 A or C AC
APP 26276888 rs2070657 C or T CT=AG
APP 26283639 rs2830000 A or C AC
APP 26291226 rs8132200 G or T GT
APP 26296475 rs7278838 A or C AC
APP 26313330 rs2830008 C or T CT
APP 26319478 rs2830012 A or G AG
APP 26329891 rs768039 A or G AG=CT
APP 26345432 rs2070655 G or T GT=AC
APP 26349119 rs2830028 G or T GT
APP 26357396 rs2830036 C or T CT
APP 26365521 rs1041420 A or G AG
APP 26376866 rs2830044 C or T CT
APP 26456132 rs4817090 C or T CT

ZNF292 gene[edit]

  • Whole genome association study of brain-wide imaging phenotypes for identifying quantitative trait loci in MCI and AD: A study of the ADNI cohort
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892122/
Two types of refined imaging genetics analysis were performed for one of the top SNPs (NXPH1, rs6463843), including a VBM analysis assessing global grey matter (GM) density and a regional analysis of target phenotypes. These focused analyses resulted in interesting imaging genetics findings about the target SNP, including an overall and regional decrease in GM density associated with TT genotype relative to the GG genotype with an increased vulnerability to this effect in AD participants.
rs6463843 (NXPH1), was selected for detailed imaging analyses since it was the only SNP strongly associated with both left and right hippocampi other than rs429358 (APOE) and rs2075650 (TOMM40). The results of a two-way ANOVA using VBM to compare the effects of baseline diagnostics group and rs6463843 (NXPH1) genotype on global GM density are shown in Fig. 4. After evaluating hippocampal GM density group means for each diagnosis-genotype group, we chose to contrast GG vs. TT (GG>TT) using all participants (n=715; 166 AD (44 TT, 78 GT, 44 GG); 346 MCI (82 TT, 170 GT, 94 GG); 203 HC (35 TT, 105 GT, 63 GG)). As shown in Fig. 4a, TT participants had significantly reduced global GM density throughout the brain relative to GG participants (p<0.01 (FDR), k=27).
  • If the allele is rs429358(C) and the same chromosome also harbors the rs7412(C) allele, the combination is known as an ApoE4 allele. The ApoE4 allele has a strong influence on the risk of Alzheimer's disease.
APOE 50103781 rs429358 C or T CT
APOE 50103919 rs7412 C or T CC

The association study between DHCR24 polymorphisms and Alzheimer's disease[edit]

  • DHCR24 55106113 rs600491 C or T TT
  • The single locus association analysis indicated that men carrying the T allele of rs600491 had an increased risk of AD (OR 1.7 95% CI 1.2-2.4; P = 0.004, Bonferroni corrected P = 0.048 with 12 tests).
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1226055/
  • The DHCR24 rs600491 genotype and allele distributions did not differ significantly between the AD and HC groups (p=0.881 for genotypes; p=0.845 for alleles). Stratification according to gender however, revealed a statistically significant association between T/T genotype and AD risk in men (AD:32.4%, HC: 16.9%; p=0.028), in contrast with the results in women (AD: 29.6%, HC: 33.8%;p=0.472). Men with the T/T genotype had a significantly increased risk for AD (OR=4.37; p=0.009)considering C/C genotype as reference category(OR=1).
http://www.elitmed.hu/upload/pdf/az_alzheimer_kor_genetikai_kockazati_tenyezoi-6195.pdf

Possible Prevention And Treatment for LOAD[edit]

  • A Potential Role of the Curry Spice Curcumin in Alzheimer’s Disease

The crucial chemical is curcumin, a compound found in the spice. Alzheimer's is linked to the build up of knots in the brain called amyloid plaques. Turmeric reduced the number of these plaques by a half. The researchers also found that turmeric had other health benefits.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1702408/
  • Picamilon (also known as nicotinoyl-GABA, Pycamilon, Pikamilon, etc) is a dietary supplement formed by

combining niacin with GABA.

http://en.wikipedia.org/wiki/Picamilon
  • Imbalance between GABAergic and Glutamatergic Transmission Impairs Adult Neurogenesis in an Animal Model of Alzheimer’s Disease
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823799/
  • Docosahexaenoic Acid Protects from Dendritic Pathology in an Alzheimer’s Disease Mouse Model
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2442162/

Alternative Treatments For LOAD[edit]

  • Alternative Treatments

The rigorous scientific research required by the U.S. Food and Drug Administration (FDA) for the approval of a prescription drug is not required by law for the marketing of dietary supplements or "medical foods." http://www.alz.org/alzheimers_disease_alternative_treatments.asp

Caprylic acid and coconut oil
Concerns
Coenzyme Q10
Coral calcium
Ginkgo biloba
Cuperzine A
Omega-3 fatty acids
Phosphatidylserine
Tramiprosate
  • Anti-oxidant, anti-glycant, and inhibitory activity against ?-amylase and ?-glucosidase of selected spices and culinary herbs
http://informahealthcare.com/doi/abs/10.3109/09637486.2010.529068

Caffeine[edit]

  • Caffeine and Coffee as Therapeutics Against Alzheimer’s Disease
http://iospress.metapress.com/content/356hp5k5k142555v/fulltext.pdf
  • Caffeine Reverses Cognitive Impairment and Decreases Brain Amyloid-? Levels in Aged Alzheimer’s Disease Mice
http://health.usf.edu/nocms/publicaffairs/now/pdfs/JAD_Arendash_Caffeine.pdf
  • Caffeine Synergizes with Another Coffee Component to Increase Plasma GCSF: Linkage to Cognitive Bene?ts in Alzheimer’s Mice
http://www5.ocn.ne.jp/~ajca/cosic23.3-23.pdf
  • Increased Cerebrospinal Fluid Production as a Possible Mechanism Underlying Caffeine's Protective Effect against Alzheimer's Disease
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109764/
  • Caffeine protects against disruptions of the blood-brain barrier in animal models of Alzheimer’s and Parkinson’s disease
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086010/
  • Caffeine protects against oxidative stress and Alzheimer’s disease-like pathology in rabbit hippocampus induced by cholesterol-enriched diet
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930139/

Tannic Acid[edit]

  • Tannic Acid is a Natural ?-secretase Inhibitor that Prevents Cognitive Impairment and Mitigates Alzheimer-like Pathology in Transgenic Mice
http://www.jbc.org/content/early/2012/01/04/jbc.M111.294025.full.pdf

Cotinine [Nicotine Metabolite] Reduces Amyloid-? Aggregation and Improves Memory in Alzheimer’s Disease Mice

http://health.usf.edu/nocms/publicaffairs/now/pdfs/JAD_Cotinine_Echeverria_etal_2011.pdf
http://en.wikipedia.org/wiki/Scotine

Medications for LOAD[edit]

    • CHOLINESTERASE INHIBITORS
http://en.wikipedia.org/wiki/Acetylcholinesterase_inhibitor
  • Aricept/Donepezil
http://en.wikipedia.org/wiki/Donepezil
  • Exelon/Rivastigmine
http://en.wikipedia.org/wiki/Rivastigmine
  • Razadyne/Galantamine
http://en.wikipedia.org/wiki/Razadyne
  • Cognex/Tacrine
http://en.wikipedia.org/wiki/Tacrine
    • NMDA GLUTAMATE RECEPTER BLOCKER
  • Axura and Akatinol/Memantine
http://en.wikipedia.org/wiki/Memantine
"...little evidence of effect in mild to moderate Alzheimer's disease."