REGIONAL SYMPOSIUM ON REGIONAL SYMPOSIUM ON ALZHEIMER’S DISEASE AND RELATED DISORDERS ALZHEIMER’S DISEASE AND RELATED DISORDERS IN THE MIDDLE EAST IN THE MIDDLE EAST Istanbul, Turkey Istanbul, Turkey October 1-2, 2005 October 1-2, 2005 Convener: Robert P. Friedland, MD Convener: Robert P. Friedland, MD LOC Chair: Murat Emre, MD LOC Chair: Murat Emre, MD www.worldeventsforum.com/ alz.htm
56
Embed
REGIONAL SYMPOSIUM ON ALZHEIMERS DISEASE AND RELATED DISORDERS IN THE MIDDLE EAST Istanbul, Turkey October 1-2, 2005 Convener: Robert P. Friedland, MD.
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
REGIONAL SYMPOSIUM ON REGIONAL SYMPOSIUM ON
ALZHEIMER’S DISEASE AND RELATED DISORDERS ALZHEIMER’S DISEASE AND RELATED DISORDERS
IN THE MIDDLE EASTIN THE MIDDLE EAST
Istanbul, TurkeyIstanbul, TurkeyOctober 1-2, 2005October 1-2, 2005Convener: Robert P. Friedland, MDConvener: Robert P. Friedland, MDLOC Chair: Murat Emre, MDLOC Chair: Murat Emre, MD
www.worldeventsforum.com/alz.htm
Gene environment interactions in Alzheimer’s Disease
Robert P. Friedland, Lindsay A. Farrer, Rivka Inzelberg, Amin Abuful, Magda Marsarwa, Rosa
Strugatsky, Clinton Baldwin, Grace Petot
Cleveland, Ohio, USA; Boston, Massachussetts USA; Hadera, Israel
227 African American AD cases, 165 non-demented sibs.
• 119 (Caucasian) and 79 (African American) AD cases and non-demented spouses.
SNP associations were evaluated using family-based association tests, generalized estimating equations and chi square tests of proportion.
• No relationships between disease and 3 TTR polymorphisms were uncovered thus far.
Farrer et al (preliminary data - unpublished)
27424463 intron rs723744
27425782 intron rs1080094
27428958 intron rs3794884
Chromosome 18
TTR and AD• TTR levels decreased in plasma and CSF in
AD patients, cor. with dementia severityRiiosen et al, 1988; Davidsson et al,1997; Serot et al,1997; Merched et al, 1998, Riisoen,1988
• In early life AD Tg mice have increased TTR expression (before ABeta deposition and neuronal loss)….also neutralization of TTR enhances AD pathology in AD Tg mice
Stein and Johnson, 2002; Stein et al, 2004
Worldwide distribution of AD
• Age-related
• Less in Asia, Africa, India
• More in African-Americans and Hispanics than Caucasians or Africans
• Few studies in the Middle East
Wadı Ara studıes• Rıvka Inzelberg, Co-Prıncıpal
Investıgator
• Populatıon based survey of genetıc and envıronmental factors
Every hereditary monarch in Europe at the beginning of the 20th century was a descendent of Edward III(Manrubia et al, 2003)
Edward III, 1312-1377
Alzheimer’s disease in Wadi Ara
• familial clustering of AD [with low Apo E e4 allele frequency, ~4%], perhaps related in inbreeding
• genetic linkages of AD to sites on chromosomes 9, 10 and 12.
• Environmental factors may include low levels of education and fish consumption, smoking, high fat diet, hypertension and physical inactivity.
Alzheimer’s disease in Africans and African
Americans• Higher e4 freq. in Africans and African -
Americans• Lower AD prevalence and incidence in
Africans and higher in African- Americans (compared to Caucasians)(Hendrie et al, 1999, Kalaria et al, 1999, Evans et al, 2000)
Obesity and Alzheimer’s disease
96 cases, 275 Controls; adjusted for year of birth, Apo E genotype, gender and education. [Petot et al, unpublished]
Dietary fat and AD• High fat diets during the 40-59 year age period were not a risk factor for AD, regardless of ApoE status,
and they may be protective.
• ApoE e4 risk for AD increased 2.7 times with high linoleic acid diets during the 40-59 year age period.
117 Cases 356 controls, adjusting for year of birth, Apo E genotype, gender and
education
Petot et al, (ANA, Sept. 2005)
Fish, PUFA and AD
• Fish consumption is linked to lower AD risk (also CAD, stroke, cancer)
(Kalmijn et al, 2000; Morris et al, 2003, Friedland, 2003)
• Dietary intake of omega 3 PUFAs influences the expression levels of many genes controlling resistance to endogenous free radicals and ABeta protein balance